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Prognostic Significance of Protein Markers in Colorectal Cancer Stratified by Mismatch Repair Status

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Colorectal Cancer

Part of the book series: Methods of Cancer Diagnosis, Therapy, and Prognosis ((HAYAT,volume 4))

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Colorectal cancer CRC is a leading cause of cancer-related mortality in North America and Western Europe. Although early stages of the disease are linked to excellent postoperative prognosis and a cure rate of 80–95%, patients with invasive cancers and lymph node metastasis have a 5-year survival rate of 25–60% (Compton and Greene, 2004). Targeted-therapy based on the individual gene or protein expression profile of the tumor is expected to improve outcome and response to chemotherapy or radiotherapy by assisting in the selection of candidate patients for specific treatment protocols (Ghadimi et al., 2005).

Colorectal cancers are classified at the molecular level into two main groups. The majority of CRCs occur sporadically 80–90% and arise through the “tumor suppressor pathway” involving sequential mutations and loss of heterozygosity in several tumor suppressor genes such as adenomatous polyposis coli (APC), deleted in colon cancer DCC, p53, and KRAS (Weitz et al., 2005). Approximately 15% of CRCs develop as a consequence of the “mutator pathway” characterized by inactivation of the DNA mismatch repair, MMR machinery leading to microsatellite instability (MSI), and immunohistochemical negativity for proteins MLH1, MSH2, and MSH6 (Jass, 2004a).

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References

  • Abetamann, V., Kern, H.F., and Elsasser, H.P. 1996. Differential expression of the hyaluronan receptors CD44 and RHAMM in human pancreatic cancer cells. Clin. Cancer Res. 2: 1607–1618.

    PubMed  CAS  Google Scholar 

  • Atkins, D., Reiffen, K.A., Tegtmeier, C.L., Winther, H., Bonato, M.S., and Storkel, S. 2004. Immunohisto-chemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J. Histochem. Cytochem. 52: 893–901.

    Article  PubMed  CAS  Google Scholar 

  • Baker, K., Chong, G., Foulkes, W.D., and Jass, J.R. 2006. Transforming growth factor-beta pathway disruption and infiltration of colorectal cancers by intraepithelial lymphocytes. Histopathology 49: 371–380.

    Article  PubMed  CAS  Google Scholar 

  • Baker, K., Zlobec, I., Tornillo, L., Terracciano, L., Jass, J.R., and Lugli, A. 2007. Differential significance of tumour infiltrating lymphocytes in sporadic mismatch repair deficient versus proficient colorectal cancers: a potential role for dysregulation of the transforming growth factor-beta pathway. Eur. J. Cancer 43: 624–631.

    Article  PubMed  CAS  Google Scholar 

  • Baldi, A., Santini, D., Russo, P., Catricala, C., Amantea, A., Picardo, M., Tatangelo, F., Botti, G., Dragonetti, E., Murace, R., Tonini, G., Natali, P.G., Baldi, F., and Paggi, M.G. 2004. Analysis of APAF-1 expression in human cutaneous melanoma progression. Exp. Dermatol. 13: 93–97.

    Article  PubMed  CAS  Google Scholar 

  • Barlund, M., Forozan, F., Kononen, J., Bubendorf, L., Chen, Y., Bittner, M.L., Torhorst, J., Haas, P., Bucher, C., Sauter, G., Kallioniemi, O.P., and Kallioniemi, A. 2000. Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. J. Natl. Cancer Inst. 92: 1252–1259.

    Article  PubMed  CAS  Google Scholar 

  • Bravou, V., Klironomos, G., Papadaki, E., Taraviras, S., and Varakis, J. 2006. ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway. J. Pathol. 208: 91–99.

    Article  PubMed  CAS  Google Scholar 

  • Campioni, M., Santini, D., Tonini, G., Murace, R., Dragonetti, E., Spugnini, E.P., and Baldi, A. 2005. Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance. Exp. Dermatol. 14: 811–818.

    Article  PubMed  CAS  Google Scholar 

  • Cheah, P.Y., Choo, P.H., Yao, J., Eu, K.W., and Seow-Choen, F. 2002. A survival-stratification model of human colorectal carcinomas with beta-catenin and p27kip1. Cancer 95: 2479–2486.

    Article  PubMed  CAS  Google Scholar 

  • Chetty, R. 2003. p27 Protein and cancers of the gastrointestinal tract and liver: an overview. J. Clin. Gastroenterol. 37: 23–27.

    Article  PubMed  CAS  Google Scholar 

  • Compton, C.C., and Greene, F.L. 2004. The staging of colorectal cancer: 2004 and beyond. CA-Cancer J. Clin. 54: 295–308.

    Article  PubMed  Google Scholar 

  • Creasy, C.L., and Chernoff, J. 1995. Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Gene 167: 303–306.

    Article  PubMed  CAS  Google Scholar 

  • Ding, Q., Xia, W., Liu, J.C., Yang, J.Y., Lee, D.F., Xia, J., Bartholomeusz, G., Li, Y., Pan, Y., Li, Z., Bargou, R.C., Qin, J., Lai, C.C., Tsai, F.J., Tsai, C.H., and Hung, M.C. 2005. Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. Mol. Cell 19: 159–170.

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara, T., Stolker, J.M., Watanabe, T., Rashid, A., Longo, P., Eshleman, J.R., Booker, S., Lynch, H.T., Jass, J.R., Green, J.S., Kim, H., Jen, J., Vogelstein, B., and Hamilton, S.R. 1998. Accumulated clonal genetic alterations in familial and sporadic colorectal carcinomas with widespread instability in micro-satellite sequences. Am. J. Pathol. 153: 1063–1078.

    PubMed  CAS  Google Scholar 

  • Ghadimi, B.M., Grade, M., Difilippantonio, M.J., Varma, S., Simon, R., Montagna, C., Fuzesi, L., Langer, C., Becker, H., Liersch, T., and Ried, T. 2005. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J. Clin. Oncol. 23: 1826–1838.

    Article  PubMed  CAS  Google Scholar 

  • Glantschnig, H., Rodan, G.A., and Reszka, A.A. 2002. Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation. J. Biol. Chem. 277: 42987–42996.

    Article  PubMed  CAS  Google Scholar 

  • Goethals, L., Perneel, C., Debucquoy, A., De Schutter, H., Borghys, D., Ectors, N., Geboes, K., McBride, W.H., and Haustermans, K.M. 2006. A new approach to the validation of tissue microarrays. J. Pathol. 208: 607–614.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, N.S., and Armin, M. 2001. Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 92: 1331–1346.

    Article  PubMed  CAS  Google Scholar 

  • Hanley, J.A. 1989. Receiver operating characteristic ROC methodology: the state of the art. Crit. Rev. Diagn. Imaging 29: 307–335.

    PubMed  CAS  Google Scholar 

  • Hao, X.P., Pretlow, T.G., Rao, J.S., and Pretlow, T.P. 2001. Beta-catenin expression is altered in human colonic aberrant crypt foci. Cancer Res. 61: 8085–8088.

    PubMed  CAS  Google Scholar 

  • Ilyas, M., Novelli, M., Wilkinson, K., Tomlinson, I.P., Abbasi, A.M., Forbes, A., and Talbot, I.C. 1997. Tumour recurrence is associated with Jass grouping but not with differences in E-cadherin expression in moderately differentiated Dukes' B colorectal cancers. J. Clin. Pathol. 50: 218–222.

    Article  PubMed  CAS  Google Scholar 

  • Jass, J.R. 2004a. HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam. Cancer 3: 93–100.

    Article  CAS  Google Scholar 

  • Jass, J.R. 2004b. Sporadic versus hereditary forms of colorectal cancer with the DNA microsatellite instability phenotype: to ‘lump’ or ‘split’? Fam. Cancer 3: 83.

    Article  CAS  Google Scholar 

  • Jass, J.R., Whitehall, V.L., Young, J., and Leggett, B.A. 2002a. Emerging concepts in colorectal neoplasia. Gastroenterology 123: 862–876.

    Article  CAS  Google Scholar 

  • Jass, J.R., Young, J., and Leggett, B.A. 2002b. Evolution of colorectal cancer: change of pace and change of direction. J. Gastroenterol. Hepatol. 17: 17–26.

    Article  Google Scholar 

  • Kane, M.F., Loda, M., Gaida, G.M., Lipman, J., Mishra, R., Goldman, H., Jessup, J.M., and Kolodner, R. 1997. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 57: 808–811.

    PubMed  CAS  Google Scholar 

  • Line, A., Slucka, Z., Stengrevics, A., Silina, K., Li, G., and Rees, R.C. 2002. Characterisation of tumour-associated antigens in colon cancer. Cancer Immunol. Immunother. 51: 574–582.

    Article  PubMed  CAS  Google Scholar 

  • Lugli, A., Zlobec, I., Gunthert, U., Minoo, P., Baker, K., Tornillo, L., Terracciano, L., and Jass, J.R. 2006a. Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer. Mod. Pathol. 19: 1302–1309.

    Article  CAS  Google Scholar 

  • Lugli, A., Zlobec, I., Minoo, P., Baker, K., Tornillo, L., Terracciano, L., and Jass, J.R. 2006b. Role of the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways downstream molecules, phosphorylated extracellular signal-regulated kinase, and phosphorylated AKT in colorectal cancer-a tissue microarray-based approach. Hum. Pathol. 37: 1022–1031.

    Article  CAS  Google Scholar 

  • Lugli, A., Zlobec, I., Baker, K., Minoo, P., Tornillo, L., Terracciano, L., and Jass, J.R. 2007a. Prognostic significance of mucins in colorectal cancer with different DNA mismatch-repair status. J. Clin. Pathol. 60: 534–539.

    Article  CAS  Google Scholar 

  • Lugli, A., Zlobec, I., Minoo, P., Baker, K., Tornillo, L., Terracciano, L., and Jass, J.R. 2007b. Prognostic significance of the wnt signalling pathway molecules APC, beta-catenin and E-cadherin in colorectal cancer: a tissue microarray-based analysis. Histopathology 50: 453–464.

    Article  CAS  Google Scholar 

  • Minoo, P., Baker, K., Goswami, R., Chong, G., Foulkes, W.D., Ruszkiewicz, A.R., Barker, M., Buchanan, D., Young, J., and Jass, J.R. 2006. Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis. Gut 55: 1467–1474.

    Article  PubMed  CAS  Google Scholar 

  • Minoo, P., Zlobec, I., Baker, K., Tornillo, L., Terracciano, L., Jass, J.R., and Lugli, A. 2007a. Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer. Am. J. Clin. Pathol. 127: 820–827.

    Article  Google Scholar 

  • Minoo, P., Zlobec, I., Baker, K., Tornillo, L., Terracciano, L., Jass, J.R., and Lugli, A. 2007b. Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer. Mod. Pathol. 20: 331–338.

    Article  CAS  Google Scholar 

  • Robinson, P.W., Green, S.J., Carter, C., Coadwell, J., and Kilshaw, P.J. 2001. Studies on transcriptional regulation of the mucosal T-cell integrin alphaE-beta7 CD103. Immunology 103: 146–154.

    Article  PubMed  CAS  Google Scholar 

  • Sauter, G., Simon, R., and Hillan, K. 2003. Tissue microarrays in drug discovery. Nat. Rev. Drug Discov. 2: 962–972.

    Article  PubMed  CAS  Google Scholar 

  • Sebolt-Leopold, J.S. 2000. Development of anti-cancer drugs targeting the MAP kinase pathway. Oncogene 19: 6594–6599.

    Article  CAS  Google Scholar 

  • Testa, J.R., and Bellacosa, A. 2001. AKT plays a central role in tumorigenesis. Proc. Natl. Acad. Sci. U. S. A. 98: 10983–10985.

    Article  PubMed  CAS  Google Scholar 

  • Theroux, S., Pereira, M., Casten, K.S., Burwell, R.D., Yeung, K.C., Sedivy, J.M., and Klysik, J. 2007. Raf kinase inhibitory protein knockout mice: expression in the brain and olfaction deficit. Brain Res. Bull. 71: 559–567.

    Article  PubMed  CAS  Google Scholar 

  • Tornillo, L., Lugli, A., Zlobec, I., Willi, N., Glatz, K., Lehmann, F., Spichtin, H.P., Maurer, R., Stoios, D., Sauter, G., and Terracciano, L. 2007. Prognostic value of cell cycle and apoptosis regulatory proteins in mismatch repair-proficient colorectal cancer: a tissue microarray-based approach. Am. J. Clin. Pathol. 127: 114–123.

    Article  PubMed  CAS  Google Scholar 

  • Turley, E.A., Noble, P.W., and Bourguignon, L.Y. 2002. Signaling properties of hyaluronan receptors. J. Biol. Chem. 277: 4589–4592.

    Article  PubMed  CAS  Google Scholar 

  • Umetani, N., Fujimoto, A., Takeuchi, H., Shinozaki, M., Bilchik, A.J., and Hoon, D.S. 2004. Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma. Oncogene 23: 8292–8300.

    Article  PubMed  CAS  Google Scholar 

  • Vogelstein, B., Fearon, E.R., Hamilton, S.R., Kern, S.E., Preisinger, A.C., Leppert, M., Nakamura, Y., White, R., Smits, A.M., and Bos, J.L. 1988. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319: 525–532.

    PubMed  CAS  Google Scholar 

  • Weinberg, R. 2007. The Biology of Cancer. Garland Science/Taylor & Francis, New York.

    Google Scholar 

  • Weitz, J., Koch, M., Debus, J., Hohler, T., Galle, P.R., and Buchler, M.W. 2005. Colorectal cancer. Lancet 365: 153–165.

    Article  PubMed  Google Scholar 

  • Young, J., Simms, L.A., Biden, K.G., Wynter, C., Whitehall, V., Karamatic, R., George, J., Goldblatt, J., Walpole, I., Robin, S.A., Borten, M.M., Stitz, R., Searle, J., McKeone, D., Fraser, L., Purdie, D.R., Podger, K., Price, R., Buttenshaw, R., Walsh, M.D., Barker, M., Leggett, B.A., and Jass, J.R. 2001. Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am. J. Pathol. 159: 2107–2116.

    PubMed  CAS  Google Scholar 

  • Zlobec, I., Steele, R., Michel, R.P., Compton, C.C., Lugli, A., and Jass, J.R. 2006. Scoring of p53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer. Mod. Pathol. 19: 1236–1242.

    Article  PubMed  CAS  Google Scholar 

  • Zlobec, I., Minoo, P., Baker, K., Haegert, D., Khetani, K., Tornillo, L., Terracciano, L., Jass, J.R., and Lugli, A. 2007a. Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer. Eur. J. Cancer 43: 1101–1107.

    Article  CAS  Google Scholar 

  • Zlobec, I., Steele, R., Terracciano, L., Jass, J.R., and Lugli, A. 2007c. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J. Clin. Pathol. 60: 1112–1116.

    Article  Google Scholar 

  • Zlobec, I., Vuong, T., Hayashi, S., Haegert, D., Tornillo, L., Terracciano, L., Lugli, A., and Jass, J. 2007b. A simple and reproducible scoring system for EGFR in colorectal cancer: application to prognosis and prediction of response to preoperative brachytherapy. Br. J. Cancer 96: 793–800.

    Article  CAS  Google Scholar 

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  1. Institute of Pathology, University Hospital of Basel, Schönbeinstrasse 40, Basel, CH-4031, Switzerland

    Inti Zlobec & Alessandro Lugli

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  1. Inti Zlobec
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  2. Alessandro Lugli
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  1. Department of Biological Sciences, Kean University, Union, NJ, USA

    M. A. Hayat

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Zlobec, I., Lugli, A. (2009). Prognostic Significance of Protein Markers in Colorectal Cancer Stratified by Mismatch Repair Status. In: Hayat, M.A. (eds) Colorectal Cancer. Methods of Cancer Diagnosis, Therapy, and Prognosis, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9545-0_14

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  • DOI: https://doi.org/10.1007/978-1-4020-9545-0_14

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