Skip to main content
SpringerLink
Log in

Cancer: Clinical Background and Key Challenges

  • Chapter
  • First Online:
Cancer Systems Biology, Bioinformatics and Medicine

Abstract

This chapter is aimed at a wide audience ranging from biologists to medical students and cancer specialists. It provides a comprehensive overview of systems approaches to the pathology and treatment of cancer. In particular, it addresses diagnosis and therapy by interconnecting various aspects of cancer at both the molecular and clinical level, and contrasts the unifying features of malignancies with the daunting diversity of cancer types, stages, and evolutionary processes during treatment. The importance is emphasized of both prevention and innovative treatments in reducing the cancer burden, and of early detection as the link between these two major areas. It sets the stage for analysis of cancer by means of systems biology, bioinformatics, and systems medicine. These methods involve the processing of cytological, histological, and imaging data, combined with genetic and expression profiling. The application of systems approaches to cancer-related clinical practice and research is discussed. The necessity is demonstrated for signalling pathways analysis to be fully integrated into grading and clinical staging of cancers, as well as into the process of discovering novel targets and biomarkers for diagnosis and prognosis. Key challenges and limitations are outlined for systems approaches to cancer, and areas are indicated where research needs to be focused in the future. Finally, pointers are provided to the paths that must be followed in order to move from a carefully controlled biological investigation, to approaches and technologies that will eventually accelerate the translation of new discoveries into prevention and clinical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, Gillies McKenna W (2008) Abeloff’s clinical oncology, 4th edn. Churchill Livingstone, UK

    Google Scholar 

  • Aebersold R, Auffray C, Baney E, Barillot E, Brazma A, Brett C, Brunak S, Butte A, Califano A, Celis J, Cufer T, Ferrell J, Galas D, Gallahan D, Gatenby R, Goldbeter A, Hace N, Henney A, Hood L, Iyengar R, Jackson V, Kallioniemi O, Klingmuller U, Kolar P, Kolch W, Kyriakopoulou C, Laplace F, Lehrach H, Marcus F, Matrisian L, Nolan G, Pelkmans L, Potti A, Sander C, Seljak M, Singer D, Sorger P, Stunnenberg H, Superti-Furga G, Uhlen M, Vidal M, Weinstein J, Wigle D, Williams M, Wolkenhauer O, Zhivotovsky B, Zinovyev A, Zupan B (2009) Report on EU-USA workshop: how systems biology can advance cancer research (27 October 2008). Mol Oncol 3(1):9–17

    Article  PubMed  Google Scholar 

  • Aitken JF, Elwood M, Baade PD, Youl P, English D (2010) Clinical whole-body skin examination reduces the incidence of thick melanomas. Int J Cancer 126(2):450–458

    Article  PubMed  CAS  Google Scholar 

  • Albertsen P (2009) Androgen deprivation in prostate cancer—step by step. N Engl J Med 360(24):2572–2574

    Article  PubMed  CAS  Google Scholar 

  • Alymani NA, Smith MD, Williams DJ, Petty RD (2010) Predictive biomarkers for personalised anti-cancer drug use: discovery to clinical implementation. Eur J Cancer 46(5):869–879

    Article  PubMed  CAS  Google Scholar 

  • Aparicio SA, Huntsman DG (2010) Does massively parallel DNA resequencing signify the end of histopathology as we know it? J Pathol 220(2):307–315

    PubMed  CAS  Google Scholar 

  • Arisio R, Cuccorese C, Accinelli G, Mano MP, Bordon R, Fessia L (1998) Role of fine-needle aspiration biopsy in breast lesions: analysis of a series of 4110 cases. Diagn Cytopathol 18(6):462–467

    Article  PubMed  CAS  Google Scholar 

  • Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, Cervantes F, Deininger M, Gratwohl A, Guilhot F, Hochhaus A, Horowitz M, Hughes T, Kantarjian H, Larson R, Radich J, Simonsson B, Silver RT, Goldman J, Hehlmann R (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 27(35):6041–6051

    Article  PubMed  CAS  Google Scholar 

  • Badve S, Nakshatri H (2009) Oestrogen-receptor-positive breast cancer: towards bridging histopathological and molecular classifications. J Clin Pathol 62(1):6–12

    Article  PubMed  CAS  Google Scholar 

  • Balch C, Houghton A, Sober A, Soong S (2003) Cutaneous melanoma, 4th edn. Quality Medical, St Louis

    Google Scholar 

  • Baselga J (2006) Targeting tyrosine kinases in cancer: the second wave. Science 312(5777):1175–1178

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Arribas J (2004) Treating cancer’s kinase ‘addiction’. Nat Med 10(8):786–787

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Swain SM (2009) Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 9(7):463–475

    Article  PubMed  CAS  Google Scholar 

  • Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, Drugge N, Ekberg L, Friesland S, Johansson KA, Lund JA, Morhed E, Nilsson K, Levin N, Paludan M, Sederholm C, Traberg A, Wittgren L, Lewensohn R (2009) Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol 27(20):3290–3296

    Article  PubMed  Google Scholar 

  • Beckman M (2006) Tumor complexity prompts caution about sequencing. J Natl Cancer Inst 98(24):1758–1759

    Article  PubMed  Google Scholar 

  • Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410

    Article  PubMed  CAS  Google Scholar 

  • Berry DA, Cronin KA, Plevritis SK, Fryback DG, Clarke L, Zelen M, Mandelblatt JS, Yakovlev AY, Habbema JD, Feuer EJ (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353(17):1784–1792

    Article  PubMed  CAS  Google Scholar 

  • Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11(3):359–377

    Article  PubMed  CAS  Google Scholar 

  • Bobola MS, Silber JR, Ellenbogen RG, Geyer JR, Blank A, Goff RD (2005) O6-methylguanine-DNA methyltransferase, O6-benzylguanine, and resistance to clinical alkylators in pediatric primary brain tumor cell lines. Clin Cancer Res 11(7):2747–2755

    Article  PubMed  CAS  Google Scholar 

  • Boffetta P, Hashibe M (2006) Alcohol and cancer. Lancet Oncol 7(2):149–156

    Article  PubMed  CAS  Google Scholar 

  • Bosman FT (1995) Prognostic value of pathological characteristics of colorectal cancer. Eur J Cancer 31A(7–8):1216–1221

    Article  PubMed  CAS  Google Scholar 

  • Boyle P, Autier P, Bartelink H, Baselga J, Boffetta P, Burn J, Burns HJ, Christensen L, Denis L, Dicato M, Diehl V, Doll R, Franceschi S, Gillis CR, Gray N, Griciute L, Hackshaw A, Kasler M, Kogevinas M, Kvinnsland S, La VC, Levi F, McVie JG, Maisonneuve P, Martin-Moreno JM, Bishop JN, Oleari F, Perrin P, Quinn M, Richards M, Ringborg U, Scully C, Siracka E, Storm H, Tubiana M, Tursz T, Veronesi U, Wald N, Weber W, Zaridze DG, Zatonski W, Zur HH (2003a) European code against cancer and scientific justification: third version. Ann Oncol 14(7):973–1005

    Article  CAS  Google Scholar 

  • Boyle P, d’Onofrio A, Maisonneuve P, Severi G, Robertson C, Tubiana M, Veronesi U (2003b) Measuring progress against cancer in Europe: has the 15% decline targeted for 2000 come about? Ann Oncol 14(8):1312–1325

    Article  CAS  Google Scholar 

  • Boyle P, Levin B (2008) World cancer report. http://www.iarc.fr/en/publications/pdfs-online/wcr/2008/index.php

  • Brenton JD, Carey LA, Ahmed AA, Caldas C (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 23(29):7350–7360

    Article  PubMed  CAS  Google Scholar 

  • Bridge RS, Rajaram V, Dehner LP, Pfeifer JD, Perry A (2006) Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: a comparison of two FISH strategies and RT-PCR in malignant round cell tumors. Mod Pathol 19(1):1–8

    Article  PubMed  CAS  Google Scholar 

  • Celis JE (2008) Editorial. Mol Oncol 2(1):1–1

    Article  Google Scholar 

  • Celis JE, Gromov P (2003) Proteomics in translational cancer research: toward an integrated approach. Cancer Cell 3(1):9–15

    Article  PubMed  CAS  Google Scholar 

  • Celis JE, Gromov P, Cabezon T, Moreira JM, Ambartsumian N, Sandelin K, Rank F, Gromova I (2004) Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics 3(4):327–344

    Article  PubMed  CAS  Google Scholar 

  • Celis JE, Gromov P, Cabezon T, Moreira JM, Friis E, Jirstrom K, Llombart-Bosch A, Timmermans-Wielenga V, Rank F, Gromova I (2008) 15-prostaglandin dehydrogenase expression alone or in combination with ACSM1 defines a subgroup of the apocrine molecular subtype of breast carcinoma. Mol Cell Proteomics 7(10):1795–1809

    Article  PubMed  CAS  Google Scholar 

  • Celis JE, Gromov P, Gromova I, Moreira JM, Cabezon T, Ambartsumian N, Grigorian M, Lukanidin E, thor Straten P, Guldberg P, Bartkova J, Bartek J, Lukas J, Lukas C, Lykkesfeldt A, Jaattela M, Roepstorff P, Bolund L, Orntoft T, Brunner N, Overgaard J, Sandelin K, Blichert-Toft M, Mouridsen H, Rank FE (2003) Integrating proteomic and functional genomic technologies in discovery-driven translational breast cancer research. Mol Cell Proteomics 2(6):369–377

    PubMed  CAS  Google Scholar 

  • Celis JE, Gromova I, Cabezon T, Gromov P, Shen T, Timmermans-Wielenga V, Rank F, Moreira JM (2007) Identification of a subset of breast carcinomas characterized by expression of cytokeratin 15: relationship between CK15+ progenitor/amplified cells and pre-malignant lesions and invasive disease. Mol Oncol 1(3):321–349

    Article  PubMed  Google Scholar 

  • Celis JE, Moreira JM, Gromova I, Cabezon T, Ralfkiaer U, Guldberg P, Straten PT, Mouridsen H, Friis E, Holm D, Rank F, Gromov P (2005) Towards discovery-driven translational research in breast cancer. FEBS J 272(1):2–15

    Article  PubMed  CAS  Google Scholar 

  • Chabner BA, Longo DL (2006) Cancer chemotherapy and biotherapy. Principles and practice, 4th edn. Lippincott Williams & Wilkins, Baltimore

    Google Scholar 

  • Chan JK (2001) The new world health organization classification of lymphomas: the past, the present and the future. Hematol Oncol 19(4):129–150

    Article  PubMed  CAS  Google Scholar 

  • Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14(5):1368–1376

    Article  PubMed  CAS  Google Scholar 

  • Chiang AC, Massague J (2008) Molecular basis of metastasis. N Engl J Med 359(26):2814–2823

    Article  PubMed  CAS  Google Scholar 

  • Clarke M, Coates AS, Darby SC, Davies C, Gelber RD, Godwin J, Goldhirsch A, Gray R, Peto R, Pritchard KI, Wood WC (2008) Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet 371(9606):29–40

    Article  PubMed  CAS  Google Scholar 

  • Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106

    PubMed  CAS  Google Scholar 

  • Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F (2005) Carcinogenicity of human papillomaviruses. Lancet Oncol 6(4):204

    Article  PubMed  Google Scholar 

  • Cohn-Cedermark G, Rutqvist LE, Andersson R, Breivald M, Ingvar C, Johansson H, Jonsson PE, Krysander L, Lindholm C, Ringborg U (2000) Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8–2.0 mm. Cancer 89(7):1495–1501

    Article  PubMed  CAS  Google Scholar 

  • Copland M, Hamilton A, Elrick LJ, Baird JW, Allan EK, Jordanides N, Barow M, Mountford JC, Holyoake TL (2006) Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107(11):4532–4539

    Article  PubMed  CAS  Google Scholar 

  • Correa Geyer F, Reis-Filho JS (2009) Microarray-based gene expression profiling as a clinical tool for breast cancer management: are we there yet? Int J Surg Pathol 17(4):285–302

    Article  PubMed  Google Scholar 

  • Costa J (2009) Systems approach to the practice of pathology: a new role for the pathologist. Arch Pathol Lab Med 133(4):524–526

    PubMed  Google Scholar 

  • Cotterill SJ, Ahrens S, Paulussen M, Jurgens HF, Voute PA, Gadner H, Craft AW (2000) Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group. J Clin Oncol 18(17):3108–3114

    PubMed  CAS  Google Scholar 

  • Cuppone F, Bria E, Carlini P, Milella M, Felici A, Sperduti I, Nistico C, Terzoli E, Cognetti F, Giannarelli D (2008) Taxanes as primary chemotherapy for early breast cancer: meta-analysis of randomized trials. Cancer 113(2):238–246

    Article  PubMed  CAS  Google Scholar 

  • Dardick I, Herrera GA (1998) Diagnostic electron microscopy of neoplasms. Hum Pathol 29(12):1335–1338

    Article  PubMed  CAS  Google Scholar 

  • Alava E de, Kawai A, Healey JH, Fligman I, Meyers PA, Huvos AG, Gerald WL, Jhanwar SC, Argani P, Antonescu CR, Pardo-Mindan FJ, Ginsberg J, Womer R, Lawlor ER, Wunder J, Andrulis I, Sorensen PH, Barr FG, Ladanyi M (1998) EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing’s sarcoma. J Clin Oncol 16(4):1248–1255

    PubMed  Google Scholar 

  • Delattre O (2008) Ewing’s tumours, genetic and cellular aspects. Pathol Biol (Paris) 56(5):257–259

    Article  PubMed  CAS  Google Scholar 

  • Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15):4429–4434

    Article  PubMed  Google Scholar 

  • Desmedt C, Ruiz-Garcia E, Andre F (2008) Gene expression predictors in breast cancer: current status, limitations and perspectives. Eur J Cancer 44(18):2714–2720

    Article  PubMed  CAS  Google Scholar 

  • DeVita VT Jr, Hellman S, Rosenberg SA (2008) Cancer: principles and practice of oncology. Lippincott Williams and Wilkins, Baltimore

    Google Scholar 

  • Doll R, Peto R, Boreham J, Sutherland I (2004) Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 328(7455):1519

    Article  PubMed  Google Scholar 

  • Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, Buyse M, Baum M, Buzdar A, Colleoni M, Coombes C, Snowdon C, Gnant M, Jakesz R, Kaufmann M, Boccardo F, Godwin J, Davies C, Peto R (2010) Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28(3):509–518

    Article  PubMed  CAS  Google Scholar 

  • Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1031–1037

    Article  PubMed  CAS  Google Scholar 

  • Duff SE, Jeziorska M, Rosa DD, Kumar S, Haboubi N, Sherlock D, O’Dwyer ST, Jayson GC (2006) Vascular endothelial growth factors and receptors in colorectal cancer: implications for anti-angiogenic therapy. Eur J Cancer 42(1):112–117

    Article  PubMed  CAS  Google Scholar 

  • Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12(1):19–23

    Article  PubMed  CAS  Google Scholar 

  • Eden P, Ritz C, Rose C, Ferno M, Peterson C (2004) “Good Old” clinical markers have similar power in breast cancer prognosis as microarray gene expression profilers. Eur J Cancer 40(12):1837–1841

    Article  PubMed  CAS  Google Scholar 

  • Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, Berlin

    Google Scholar 

  • Ehrlich Y, Brames MJ, Beck SD, Foster RS, Einhorn LH (2010) Long-term follow-up of Cisplatin combination chemotherapy in patients with disseminated nonseminomatous germ cell tumors: is a postchemotherapy retroperitoneal lymph node dissection needed after complete remission? J Clin Oncol 28(4):531–536

    Article  PubMed  CAS  Google Scholar 

  • Elston C, Ellis I (1998) Systemic pathology: the breast. Elsevier, Churchill Livingstone, London

    Google Scholar 

  • Espina V, Heiby M, Pierobon M, Liotta LA (2007) Laser capture microdissection technology. Expert Rev Mol Diagn 7(5):647–657

    Article  PubMed  CAS  Google Scholar 

  • Esteller M (2008) Epigenetics in cancer. N Engl J Med 358(11):1148–1159

    Article  PubMed  CAS  Google Scholar 

  • Faratian D, Bartlett J (2008) Predictive markers in breast cancer—the future. Histopathology 52(1):91–98

    Article  PubMed  CAS  Google Scholar 

  • Fass L (2008) Imaging and cancer: a review. Mol Oncol 2(2):115–152

    Article  PubMed  Google Scholar 

  • Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767

    Article  PubMed  CAS  Google Scholar 

  • Fellinger EJ, Garin-Chesa P, Su SL, DeAngelis P, Lane JM, Rettig WJ (1991) Biochemical and genetic characterization of the HBA71 Ewing’s sarcoma cell surface antigen. Cancer Res 51(1):336–340

    PubMed  CAS  Google Scholar 

  • Fenoglio-Preiser CM, Noffsinger AE, Stemmermann GN (1999) Gastrointestinal pathology: an atlas and text. Lippincott Williams & Wilkins, Baltimore

    Google Scholar 

  • Ferlay J, Parkin DM, Steliarova-Foucher E (2010a) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46(4):765–781

    Article  CAS  Google Scholar 

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010b) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Google Scholar 

  • Fletcher SW, Elmore JG (2003) Clinical practice. Mammographic screening for breast cancer. N Engl J Med 348(17):1672–1680

    Google Scholar 

  • Folpe AL, Goldblum JR, Rubin BP, Shehata BM, Liu W, Dei Tos AP, Weiss SW (2005) Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 29(8):1025–1033

    PubMed  Google Scholar 

  • Francisci S, Capocaccia R, Grande E, Santaquilani M, Simonetti A, Allemani C, Gatta G, Sant M, Zigon G, Bray F, Janssen-Heijnen M (2009) The cure of cancer: a European perspective. Eur J Cancer 45(6):1067–1079

    Article  PubMed  Google Scholar 

  • Franklin W, Muller KM, Wistuba II, Sozzi G, Geisinger K, Brambilla E, Lam S, Gazdar A, Hirsch FR (2004) Squamous dysplasia and carcinoma in situ. Pathology and genetics of tumours of the lung, pleura, thymus and heart. WHO—IARC press, Lyon

    Google Scholar 

  • Gravendeel LA, Kouwenhoven MC, Gevaert O, Rooi JJ de, Stubbs AP, Duijm JE, Daemen A, Bleeker FE, Bralten LB, Kloosterhof NK, De MB, Eilers PH, Spek PJ van der, Kros JM, Sillevis Smitt PA, Bent MJ van den, French PJ (2009) Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res 69(23):9065–9072

    Article  PubMed  CAS  Google Scholar 

  • Hahn WC, Weinberg RA (2002) Modelling the molecular circuitry of cancer. Nat Rev Cancer 2(5):331–341

    Article  PubMed  CAS  Google Scholar 

  • Haioun C, Itti E, Rahmouni A, Brice P, Rain JD, Belhadj K, Gaulard P, Garderet L, Lepage E, Reyes F, Meignan M (2005) [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood 106(4):1376–1381

    Article  PubMed  CAS  Google Scholar 

  • Hamilton SR, Aaltonen LA (2000) Pathology & genetics of tumours of the digestive system. WHO—IARCPress, Lyon

    Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  PubMed  CAS  Google Scholar 

  • Hansen RJ, Nagasubramanian R, Delaney SM, Samson LD, Dolan ME (2007) Role of O6-methylguanine-DNA methyltransferase in protecting from alkylating agent-induced toxicity and mutations in mice. Carcinogenesis 28(5):1111–1116

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa T, Hirose T, Ayala AG, Ito S, Tomaru U, Matsuno Y, Shimoda T, Hirohashi S (2001) Adult neuroblastoma of the retroperitoneum and abdomen: clinicopathologic distinction from primitive neuroectodermal tumor. Am J Surg Pathol 25(7):918–924

    Article  PubMed  CAS  Google Scholar 

  • Hayes BD, Quinn CM (2009) Pathology of B3 lesions of the breast. Diagnostic Histopathol 15(10):459–469

    Article  Google Scholar 

  • Heinrich MC, Corless CL (2004) Targeting mutant kinases in gastrointestinal stromal tumors: a paradigm for molecular therapy of other sarcomas. Cancer Treat Res 120:129–150

    Article  PubMed  CAS  Google Scholar 

  • Heinrich MC, Corless CL, Demetri GD, Blanke CD, Mehren von M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342–4349

    Article  PubMed  CAS  Google Scholar 

  • Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380

    Article  PubMed  CAS  Google Scholar 

  • Hoos A, Stojadinovic A, Mastorides S, Urist MJ, Polsky D, Di Como CJ, Brennan MF, Cordon-Cardo C (2001) High Ki-67 proliferative index predicts disease specific survival in patients with high-risk soft tissue sarcomas. Cancer 92(4):869–874

    Article  PubMed  CAS  Google Scholar 

  • Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY (1988) Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72(2):567–572

    PubMed  CAS  Google Scholar 

  • Hutter RV, Sobin LH (1986) A universal staging system for cancer of the colon and rectum. Let there be light. Arch Pathol Lab Med 110(5):367–368

    PubMed  CAS  Google Scholar 

  • Ingoldsby H, Callagy G (2009) Pathology of minimal metastatic disease in sentinel lymph nodes in breast cancer. Diagn Histopathol 15(10):470–477

    Article  Google Scholar 

  • Jakel O, Karger CP, Debus J (2008) The future of heavy ion radiotherapy. Med Phys 35(12):5653–5663

    Article  PubMed  CAS  Google Scholar 

  • Jass JR (2007) Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 50(1):113–130

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Lloyd RV (1997) In situ hybridization: methods and applications. J Clin Lab Anal 11(1):2–9

    Article  PubMed  CAS  Google Scholar 

  • Kallioniemi OP, Wagner U, Kononen J, Sauter G (2001) Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet 10(7):657–662

    Article  PubMed  CAS  Google Scholar 

  • Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6(5):392–401

    Article  PubMed  CAS  Google Scholar 

  • Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14):2137–2150

    Article  PubMed  Google Scholar 

  • Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O’Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346(9):645–652

    Article  PubMed  CAS  Google Scholar 

  • Kauer M, Ban J, Kofler R, Walker B, Davis S, Meltzer P, Kovar H (2009) A molecular function map of Ewing’s sarcoma. PLoS One 4(4):e5415

    Article  PubMed  CAS  Google Scholar 

  • Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358(19):2039–2049

    Article  PubMed  CAS  Google Scholar 

  • Khan J, Wei JS, Ringner M, Saal LH, Ladanyi M, Westermann F, Berthold F, Schwab M, Antonescu CR, Peterson C, Meltzer PS (2001) Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nat Med 7(6):673–679

    Article  PubMed  CAS  Google Scholar 

  • Kovar H, Jug G, Aryee DN, Zoubek A, Ambros P, Gruber B, Windhager R, Gadner H (1997) Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors. Oncogene 15(18):2225–2232

    Article  PubMed  CAS  Google Scholar 

  • Kreeger PK, Lauffenburger DA (2010) Cancer systems biology: a network modeling perspective. Carcinogenesis 31(1):2–8

    Article  PubMed  CAS  Google Scholar 

  • Ladanyi M (1995) The emerging molecular genetics of sarcoma translocations. Diagn Mol Pathol 4(3):162–173

    Article  PubMed  CAS  Google Scholar 

  • Lango MN (2009) Multimodal treatment for head and neck cancer. Surg Clin North Am 89(1):43–52

    Article  PubMed  Google Scholar 

  • Laubenbacher R, Hower V, Jarrah A, Torti SV, Shulaev V, Mendes P, Torti FM, Akman S (2009) A systems biology view of cancer. Biochim Biophys Acta 1796(2):129–139

    PubMed  CAS  Google Scholar 

  • Levitt SH, Perez CA, Hui S, Purdy JA (2008) Evolution of computerized radiotherapy in radiation oncology: potential problems and solutions. Int J Radiat Oncol Biol Phys 70(4):978–986

    Article  Google Scholar 

  • Levitt SH, Purdy JA, Perez CA, Vijayakumar S (2006) Technical basis of radiation therapy. Practical clinical applications, 4th edn. Lippincott Williams & Wilkins, Baltimore

    Book  Google Scholar 

  • Liu CL, Prapong W, Natkunam Y, Alizadeh A, Montgomery K, Gilks CB, Rijn M van de (2002) Software tools for high-throughput analysis and archiving of immunohistochemistry staining data obtained with tissue microarrays. Am J Pathol 161(5):1557–1565

    Article  PubMed  CAS  Google Scholar 

  • Llombart-Bosch A (2001) De la anatomia patologica estructural a la patologia molecular. Discurso de Recepcion. Real Academia de Medicina de la Comunidad Valenciana. RAMCV Press, Valencia, Spain

    Google Scholar 

  • Llombart-Bosch A, Contesso G, Peydro-Olaya A (1996) Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone. Semin Diagn Pathol 13(3):153–170

    PubMed  CAS  Google Scholar 

  • Llombart-Bosch A, Machado I, Navarro S, Bertoni F, Bacchini P, Alberghini M, Karzeladze A, Savelov N, Petrov S, varado-Cabrero I, Mihaila D, Terrier P, Lopez-Guerrero JA, Picci P (2009) Histological heterogeneity of Ewing’s sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch 455(5):397–411

    Article  PubMed  CAS  Google Scholar 

  • Llombart-Bosch A, Navarro S (2001) Immunohistochemical detection of EWS and FLI-1 proteinss in Ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99 (MIC-2) expression. Appl Immunohistochem Mol Morphol 9(3):255–260

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Guerrero JA, Machado I, Scotlandi K, Noguera R, Pellin A, Navarro S, Serra M, Calabuig-Farinas S, Picci P, Llombart-Bosch A (2011) Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing’s sarcoma family of tumors. Int J Cancer 128(5):1139–1150

    Google Scholar 

  • Lopez-Guerrero JA, Llombart-Cussac A, Noguera R, Navarro S, Pellin A, Almenar S, Vazquez-Alvadalejo C, Llombart-Bosch A (2006) HER2 amplification in recurrent breast cancer following breast-conserving therapy correlates with distant metastasis and poor survival. Int J Cancer 118(7):1743–1749

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Guerrero JA, Pellin A, Noguera R, Carda C, Llombart-Bosch A (2001) Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors. Lab Invest 81(6):803–814

    Article  PubMed  CAS  Google Scholar 

  • Lynch HT, la Chapelle A de (2003) Hereditary colorectal cancer. N Engl J Med 348(10):919–932

    Article  PubMed  CAS  Google Scholar 

  • Machado I, Noguera R, Pellin A, Lopez-Guerrero JA, Piqueras M, Navarro S, Llombart-Bosch A (2009) Molecular diagnosis of Ewing sarcoma family of tumors: a comparative analysis of 560 cases with FISH and RT-PCR. Diagn Mol Pathol 18(4):189–199

    Article  PubMed  CAS  Google Scholar 

  • Madarnas Y, Trudeau M, Franek JA, McCready D, Pritchard KI, Messersmith H (2008) Adjuvant/neoadjuvant trastuzumab therapy in women with HER-2/neu-overexpressing breast cancer: a systematic review. Cancer Treat Rev 34(6):539–557

    Article  CAS  Google Scholar 

  • Marie JP, Zittoun R, Sikic BI (1991) Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. Blood 78(3):586–592

    PubMed  CAS  Google Scholar 

  • Markowitz SD, Bertagnolli MM (2009) Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 361(25):2449–2460

    Article  PubMed  CAS  Google Scholar 

  • McCafferty MPJ, Healy NA, Kerin MJ (2009) Breast cancer subtypes and molecular biomarkers. Diagn Histopathol 15(10):485–489

    Article  Google Scholar 

  • Meara RS, Cangiarella J, Simsir A, Horton D, Eltoum I, Chhieng DC (2007) Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl-2, Ki-67 and p53. Cytopathology 18(5):283–289

    Article  PubMed  CAS  Google Scholar 

  • Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6(6):449–458

    Article  PubMed  CAS  Google Scholar 

  • Meyer T, Hart IR (1998) Mechanisms of tumour metastasis. Eur J Cancer 34(2):214–221

    Article  PubMed  CAS  Google Scholar 

  • Nagtegaal ID, Krieken JH van (2002) The role of pathologists in the quality control of diagnosis and treatment of rectal cancer-an overview. Eur J Cancer 38(7):964–972

    Article  PubMed  CAS  Google Scholar 

  • Naora H, Montell DJ (2005) Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat Rev Cancer 5(5):355–366

    Article  CAS  Google Scholar 

  • Natkunam Y, Mason DY (2006) Prognostic immunohistologic markers in human tumors: why are so few used in clinical practice? Lab Invest 86(8):742–747

    Article  PubMed  CAS  Google Scholar 

  • Navarro S, Giraudo P, Karseladze AI, Smirnov A, Petrovichev N, Savelov N, Varado-Cabrero I, Llombart-Bosch A (2007) Immunophenotypic profile of biomarkers related to anti-apoptotic and neural development pathways in the Ewing’s family of tumors (EFT) and their therapeutic implications. Anticancer Res 27(4B):2457–2463

    PubMed  CAS  Google Scholar 

  • Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9(4):274–284

    Article  PubMed  CAS  Google Scholar 

  • Nilsson G, Wang M, Wejde J, Kreicbergs A, Larsson O (1999) Detection of EWS/FLI-1 by immunostaining. An adjunctive tool in diagnosis of Ewing’s sarcoma and primitive neuroectodermal tumour on cytological samples and paraffin-embedded archival material. Sarcoma 3(1):25–32

    Article  PubMed  CAS  Google Scholar 

  • Nirmalanandhan VS, Sittampalam GS (2009) Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges. J Biomol Screen 14(7):755–768

    Article  PubMed  CAS  Google Scholar 

  • O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348(11):994–1004

    Article  PubMed  Google Scholar 

  • O’Shaughnessy JA (2006) Molecular signatures predict outcomes of breast cancer. N Engl J Med 355(6):615–617

    Article  PubMed  Google Scholar 

  • Ordonez NG, Mackay B (1998) Electron microscopy in tumor diagnosis: indications for its use in the immunohistochemical era. Hum Pathol 29(12):1403–1411

    Article  CAS  Google Scholar 

  • Parham DM, Hijazi Y, Steinberg SM, Meyer WH, Horowitz M, Tzen CY, Wexler LH, Tsokos M (1999) Neuroectodermal differentiation in Ewing’s sarcoma family of tumors does not predict tumor behavior. Hum Pathol 30(8):911–918

    Article  PubMed  CAS  Google Scholar 

  • Parkin DM (2004) International variation. Oncogene 23(38):6329–6340

    Article  PubMed  CAS  Google Scholar 

  • Pass HI, Mitchell JB, Johnson DH, Turrisi AT, Minna JD (2000) Lung cancer: principles and practice, 2nd edn. Lippincott Williams & Wilkins, Baltimore

    Google Scholar 

  • Patz EF Jr, Campa MJ, Gottlin EB, Kusmartseva I, Guan XR, Herndon JE (2007) Panel of serum biomarkers for the diagnosis of lung cancer. J Clin Oncol 25(35):5578–5583

    Article  PubMed  Google Scholar 

  • Payne SJ, Bowen RL, Jones JL, Wells CA (2008) Predictive markers in breast cancer—the present. Histopathology 52(1):82–90

    Article  PubMed  CAS  Google Scholar 

  • Perou CM, Sorlie T, Eisen MB, Rijn M van de, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752

    Article  PubMed  CAS  Google Scholar 

  • Pinero-Madrona A, Polo-Garcia L, Onso-Romero JL, Salinas-Ramos J, Canteras-Jordana M, Sola-Perez J, Galindo-Fernandez PJ, Illana-Moreno J, Bermejo-Lopez J, Navarrete-Montoya A, Parrilla-Paricio P (2008) Immunohistochemical characterisation of breast cancer: towards a new clasification? Cir Esp 84(3):138–145

    Article  PubMed  Google Scholar 

  • Pinkerton R, Matthay K, Shankar AG (2007) Evidence-based pediatric oncology, 2nd edn. Blackwell, Oxford

    Book  Google Scholar 

  • Pleasance ED, Stephens PJ, O’Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, Davies HR, Ordonez GR, Mudie LJ, Latimer C, Edkins S, Stebbings L, Chen L, Jia M, Leroy C, Marshall J, Menzies A, Butler A, Teague JW, Mangion J, Sun YA, McLaughlin SF, Peckham HE, Tsung EF, Costa GL, Lee CC, Minna JD, Gazdar A, Birney E, Rhodes MD, McKernan KJ, Stratton MR, Futreal PA, Campbell PJ (2010) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463(7278):184–190

    Article  PubMed  CAS  Google Scholar 

  • Ponten J (2001) Cell biology of precancer. Eur J Cancer 37(Suppl 8):97–113

    Article  Google Scholar 

  • Rakha EA, Putti TC, bd El-Rehim DM, Paish C, Green AR, Powe DG, Lee AH, Robertson JF, Ellis IO (2006) Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 208(4):495–506

    Article  CAS  Google Scholar 

  • Ransohoff DF (2009) Promises and limitations of biomarkers. Recent Results Cancer Res 181:55–59

    Article  PubMed  Google Scholar 

  • Reis-Filho JS, Westbury C, Pierga JY (2006) The impact of expression profiling on prognostic and predictive testing in breast cancer. J Clin Pathol 59(3):225–231

    Article  PubMed  CAS  Google Scholar 

  • Richards MA (2009) The size of the prize for earlier diagnosis of cancer in England. Br J Cancer 101(Suppl 2):S125–S129

    Article  PubMed  Google Scholar 

  • Ringborg U, Bergqvist D, Brorsson B, Cavallin-Stahl E, Ceberg J, Einhorn N, Frodin JE, Jarhult J, Lamnevik G, Lindholm C, Littbrand B, Norlund A, Nylen U, Rosen M, Svensson H, Moller TR (2003) The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001—summary and conclusions. Acta Oncol 42(5–6):357–365

    Article  PubMed  Google Scholar 

  • Rosai J (2001) The continuing role of morphology in the molecular age. Mod Pathol 14(3):258–260

    Article  PubMed  CAS  Google Scholar 

  • Rosai J (2007) Why microscopy will remain a cornerstone of surgical pathology. Lab Invest 87(5):403–408

    Article  PubMed  Google Scholar 

  • Rosai J, Ackerman LV (1996) Ackerman’s surgical pathology. CRC Press, Boca Raton

    Google Scholar 

  • Saad RS, Kordunsky L, Liu YL, Denning KL, Kandil HA, Silverman JF (2006) Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol 19(10):1317–1323

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Garcia I (2009) The crossroads of oncogenesis and metastasis. N Engl J Med 360(3):297–299

    Article  PubMed  CAS  Google Scholar 

  • Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550

    Article  PubMed  CAS  Google Scholar 

  • Sara H, Kallioniemi O, Nees M (2010) A decade of cancer gene profiling: from molecular portraits to molecular function. Methods Mol Biol 576:61–87

    Article  PubMed  CAS  Google Scholar 

  • Sarkaria JN, Bristow RG (2008) Overview of cancer molecular radiobiology. Cancer Treat Res 139:117–133

    PubMed  CAS  Google Scholar 

  • Schoenberg Fejzo M, Slamon DJ (2001) Frozen tumor tissue microarray technology for analysis of tumor RNA, DNA, and proteins. Am J Pathol 159(5):1645–1650

    Article  PubMed  CAS  Google Scholar 

  • Sharma R, Hamilton A, Beith J (2008) LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women. Cochrane Database Syst Rev (4):CD004562

    Google Scholar 

  • Shepherd FA, Rodrigues PJ, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, Kooten M van, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132

    Article  PubMed  CAS  Google Scholar 

  • Shergill IS, Shergill NK, Arya M, Patel HR (2004) Tissue microarrays: a current medical research tool. Curr Med Res Opin 20(5):707–712

    Article  PubMed  CAS  Google Scholar 

  • Shia J, Ellis NA, Paty PB, Nash GM, Qin J, Offit K, Zhang XM, Markowitz AJ, Nafa K, Guillem JG, Wong WD, Gerald WL, Klimstra DS (2003) Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol 27(11):1407–1417

    Article  PubMed  Google Scholar 

  • Simunovic M, Smith AJ, Heald RJ (2009) Rectal cancer surgery and regional lymph nodes. J Surg Oncol 99(4):256–259

    Article  CAS  Google Scholar 

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182

    Article  PubMed  CAS  Google Scholar 

  • Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sanchez RP, Piccart-Gebhart MJ (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36

    Article  PubMed  CAS  Google Scholar 

  • Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, Oxford

    Google Scholar 

  • Sorlie T, Perou CM, Fan C, Geisler S, Aas T, Nobel A, Anker G, Akslen LA, Botstein D, Borresen-Dale AL, Lonning PE (2006) Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer. Mol Cancer Ther 5(11):2914–2918

    Article  PubMed  CAS  Google Scholar 

  • Spira A, Ettinger DS (2004) Multidisciplinary management of lung cancer. N Engl J Med 350(4):379–392

    Article  PubMed  CAS  Google Scholar 

  • Tang P, Skinner KA, Hicks DG (2009) Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? Diagn Mol Pathol 18(3):125–132

    Article  PubMed  CAS  Google Scholar 

  • Tavassoli FA, Devilee P (2003) Pathology & genetics: tumours of the breast and female genital organs. IARC press—WHO, Lyon

    Google Scholar 

  • Taylor CR, Cote RJ (1997) Immunohistochemical markers of prognostic value in surgical pathology. Histol Histopathol 12(4):1039–1055

    PubMed  CAS  Google Scholar 

  • Terrier P, Henry-Amar M, Triche TJ, Horowitz ME, Terrier-Lacombe MJ, Miser JS, Kinsella TJ, Contesso G, Llombart-Bosch A (1995) Is neuro-ectodermal differentiation of Ewing’s sarcoma of bone associated with an unfavourable prognosis? Eur J Cancer 31A(3):307–314

    Article  PubMed  CAS  Google Scholar 

  • Thun MJ, Henley SJ, Burns D, Jemal A, Shanks TG, Calle EE (2006) Lung cancer death rates in lifelong nonsmokers. J Natl Cancer Inst 98(10):691–699

    Article  PubMed  Google Scholar 

  • Tlsty TD, Coussens LM (2006) Tumor stroma and regulation of cancer development. Annu Rev Pathol 1:119–150

    Article  PubMed  CAS  Google Scholar 

  • Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) Pathology & genetics of tumours of the lung, pleura, thymus and heart. IARC press—WHO, Lyon

    Google Scholar 

  • Trigg ME, Sather HN, Reaman GH, Tubergen DG, Steinherz PG, Gaynon PS, Uckun FM, Hammond GD (2008) Ten-year survival of children with acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Leuk Lymphoma 49(6):1142–1154

    Article  PubMed  Google Scholar 

  • Ueda T, Aozasa K, Tsujimoto M, Ohsawa M, Uchida A, Aoki Y, Ono K, Matsumoto K (1989) Prognostic significance of Ki-67 reactivity in soft tissue sarcomas. Cancer 63(8):1607–1611

    Article  PubMed  CAS  Google Scholar 

  • Valk PJ, Verhaak RG, Beijen MA, Erpelinck CA, Barjesteh van Waalwijk van Doorn-Khosrovani, Boer JM, Beverloo HB, Moorhouse MJ, Spek PJ van der, Lowenberg B, Delwel R (2004) Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med 350(16):1617–1628

    Article  PubMed  CAS  Google Scholar 

  • Oosterom AT van, Judson I, Verweij J, Stroobants S, di Donato PE, Dimitrijevic S, Martens M, Webb A, Sciot R, Van GM, Silberman S, Nielsen OS (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358(9291):1421–1423

    Article  PubMed  Google Scholar 

  • Verellen D, Ridder MD, Linthout N, Tournel K, Soete G, Storme G (2007) Innovations in image-guided radiotherapy. Nat Rev Cancer 7(12):949–960

    Article  PubMed  CAS  Google Scholar 

  • Watt FM, Driskell RR (2010) The therapeutic potential of stem cells. Philos Trans R Soc Lond B Biol Sci 365(1537):155–163

    Article  PubMed  Google Scholar 

  • Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R (2003) Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 21(1):16–19

    Article  PubMed  CAS  Google Scholar 

  • Weidner N, Tjoe J (1994) Immunohistochemical profile of monoclonal antibody O13: antibody that recognizes glycoprotein p30/32MIC2 and is useful in diagnosing Ewing’s sarcoma and peripheral neuroepithelioma. Am J Surg Pathol 18(5):486–494

    Article  PubMed  CAS  Google Scholar 

  • Weigelt B, Peterse JL, van’t Veer LJ (2005) Breast cancer metastasis: markers and models. Nat Rev Cancer 5(8):591–602

    Article  PubMed  CAS  Google Scholar 

  • Weinberg RA (2007) Biology of cancer. Garland Science, London

    Google Scholar 

  • Whitehead R (1994) Gastrointestinal and oesohageal pathology. Churchill Livingstone, London

    Google Scholar 

  • Witz IP (2009) The tumor microenvironment: the making of a paradigm. Cancer Microenviron 2(Suppl 1):9–17

    Article  PubMed  Google Scholar 

  • Yamanaka R, Saya H (2009) Molecularly targeted therapies for glioma. Ann Neurol 66(6):717–729

    Article  PubMed  CAS  Google Scholar 

  • Zambelli D, Zuntini M, Nardi F, Manara MC, Serra M, Landuzzi L, Lollini PL, Ferrari S, Alberghini M, Llombart-Bosch A, Piccolo E, Iacobelli S, Picci P, Scotlandi K (2010) Biological indicators of prognosis in Ewing’s sarcoma: an emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP). Int J Cancer 126(1):41–52

    Article  PubMed  CAS  Google Scholar 

  • Zhan F, Tian E, Bumm K, Smith R, Barlogie B, Shaughnessy J Jr (2003) Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late-stage B-cell development. Blood 101(3):1128–1140

    Article  CAS  Google Scholar 

  • Zhang X, Li L, Wei D, Yap Y, Chen F (2007) Moving cancer diagnostics from bench to bedside. Trends Biotechnol 25(4):166–173

    Article  PubMed  CAS  Google Scholar 

  • Zoubek A, Dockhorn-Dworniczak B, Delattre O, Christiansen H, Niggli F, Gatterer-Menz I, Smith TL, Jurgens H, Gadner H, Kovar H (1996) Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J Clin Oncol 14(4):1245–1251

    Google Scholar 

Download references

Acknowledgements

We are indebted to Laila Fischer for expert secretarial assistance. This work was supported by the IVO Cancer Institute and the EuroBoNeT consortium, a network of excellence granted by the European Commission for studying the pathology and genetics of bone tumours (to ALLB), the Stockholm Cancer Society (to UR), and the Danish Cancer Society, the Danish Medical Research Council, and the John and Birthe Meyer Foundation (to JEC).

Author information

Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of Valencia, Valencia, Spain

    Dr. Antonio Llombart-Bosch MD

  2. Cancer Center Karolinska, Stockholm, Sweden

    Prof. Ulrik Ringborg MD, PhD

  3. Department of Haematology, Catholic University and Immuno-Oncology Lab, IRCCS San Raffaele, Rome, Italy

    Dr. Sergio Rutella MD, PhD

  4. Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark

    Dr. Julio E. Celis

Authors
  1. Dr. Antonio Llombart-Bosch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prof. Ulrik Ringborg MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dr. Sergio Rutella MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dr. Julio E. Celis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Llombart-Bosch MD .

Editor information

Editors and Affiliations

  1. Via vi Valcannuta 247, Rome, 00166, Italy

    Alfredo Cesario

  2. Rue Ed. Dereume 72, Rixensart, 1330, Belgium

    Frederick Marcus

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Llombart-Bosch, A., Ringborg, U., Rutella, S., Celis, J. (2011). Cancer: Clinical Background and Key Challenges. In: Cesario, A., Marcus, F. (eds) Cancer Systems Biology, Bioinformatics and Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1567-7_2

Download citation

Publish with us

Policies and ethics

Search

Navigation