Abstract
Ovarian cancer is the fifth most common cancer in women and is the most lethal of all gynecologic cancers. Early-stage ovarian cancer is curable while women who are diagnosed with advanced ovarian cancer continue to have poor long-term survival due to recurrence of disease. Unfortunately, most women are diagnosed with advanced-stage disease. Early detection is a primary objective for clinicians and scientists, yet single modality (CA-125, transvaginal ultrasound) screening tests have been ineffective. More recent novel approaches combining modalities and utilizing serial serum sampling are being tested and hold great promise. In addition, the recent application of proteomics to this clinical question has the potential to identify new and important biotargets.
Unfortunately, the majority of ovarian cancer patients have advanced-stage disease, and although most will die of their disease, their survival is quite heterogenous. The ability to stratify patients according to prognosis could help guide therapy. The current “gold standard” for prognosis uses patient, surgical, and tumor characteristics, yet these have the tendency to be notoriously inaccurate. This prognostic uncertainty and the drive to identify predictive factors by which we can select novel and targeted therapy have stimulated researchers to look beyond traditional markers and test and validate molecular and genomic biomarkers, which are anticipated to soon complement or even eclipse traditional factors clarifying prognosis and select treatments. For patients with advanced-stage disease, a multitude of prognostic factors have been characterized. While promising, none of these biotargets have been validated at present to be clinically useful. More recent application of genomic technologies is likely to yield clinically relevant signatures and/or biotargets which will provide the basis for personalization of care for these patients.
Keywords
- Vascular Endothelial Growth Factor
- Ovarian Cancer
- Epithelial Ovarian Cancer
- Ovarian Cancer Patient
- Human Epididymis Protein
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Fleming GF, Ronnett BM, Seidman J, Zaino RJ, Rubin SC. Epithelial Ovarian Cancer. In: Markman M, Barakat RR, Randall ME, editors. Principles and practice of gynecologic oncology. 5th ed. Baltimore: Lippincott Williams & Wilkins; 2009. p. 763–835.
Bast Jr RC, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9:415–28.
Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet. 2009;374:1371–82.
Helzlsouer KJ, Bush TL, Alberg AJ, Bass KM, Zacur H, Comstock GW. Prospective study of serum CA-125 levels as markers of ovarian cancer. JAMA. 1993;269:1123–6.
Jellum E, Andersen A, Lund-Larsen P, Theodorsen L, Orjasaeter H. Experiences of the Janus Serum Bank in Norway. Environ Health Perspect. 1995;103 Suppl 3:85–8.
Hellstrom I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63:3695–700.
Rosen DG, Wang L, Atkinson JN, et al. Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol. 2005;99:267–77.
Fujirebio Diagnostics I. HE4 EIA [package insert]. Malvern, PA; 2008.
Campbell S, Bhan V, Royston P, Whitehead MI, Collins WP. Transabdominal ultrasound screening for early ovarian cancer. BMJ. 1989;299:1363–7.
Van Nagell Jr JR, DePriest PD, Reedy MB, et al. The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer. Gynecol Oncol. 2000;77:350–6.
Guerriero S, Alcazar JL, Ajossa S, et al. Transvaginal color Doppler imaging in the detection of ovarian cancer in a large study population. Int J Gynecol Cancer. 2010;20:781–6.
Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002;359:572–7.
Giljohann DA, Mirkin CA. Drivers of biodiagnostic development. Nature. 2009;462:461–4.
Cane P, Azen C, Lopez E, Platt LD, Karlan BY. Tumor marker trends in asymptomatic women at risk for ovarian cancer: relevance for ovarian cancer screening. Gynecol Oncol. 1995;57:240–5.
Skates SJ, Menon U, MacDonald N, et al. Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women. J Clin Oncol. 2003;21:206s–10.
Lu KH, Skates SJ, Bevers TB, et al. A prospective U.S. ovarian cancer screening study using the risk of ovarian cancer algorithm (ROCA). J Clin Oncol. 2010;28(suppl). abstr 5003.
Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10:327–40.
Nolen B, Velikokhatnaya L, Marrangoni A, et al. Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol. 2010;117:440–5.
Jacob F, Meier M, Caduff R, et al. No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecol Oncol. 2011;121:487–91.
Andersen MR, Goff BA, Lowe KA, et al. Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. Gynecol Oncol. 2010;116:378–83.
Moore RG, Miller MC, Disilvestro P, et al. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol. 2011;118:280–8.
Van Gorp T, Cadron I, Despierre E, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 2011;104:863–70.
Moore RG, McMeekin DS, Brown AK, et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 2009;112:40–6.
Zhang Z, Chan DW. The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomarkers Prev. 2010;19:2995–9.
Ueland FR, Desimone CP, Seamon LG, et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol. 2011;117:1289–97.
Holschneider C, Berek J. Ovarian cancer: epidemiology, biology and prognostic factors. Semin Surg Oncol. 2000;19(1):3–10.
Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol. 2009;112:265–74.
Kaku T, Ogawa S, Kawano Y, et al. Histological classification of ovarian cancer. Med Electron Microsc. 2003;36:9–17.
Kobel M, Kalloger SE, Santos JL, Huntsman DG, Gilks CB, Swenerton KD. Tumor type and substage predict survival in stage I and II ovarian carcinoma: insights and implications. Gynecol Oncol. 2010;116:50–6.
Thigpen T, Brady MF, Omura GA, et al. Age as a prognostic factor in ovarian carcinoma. The Gynecologic Oncology Group experience. Cancer. 1993;71:606–14.
Omura GA, Brady MF, Homesley HD, et al. Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J Clin Oncol. 1991;9:1138–50.
Cooper BC, Sood AK, Davis CS, et al. Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer. Obstet Gynecol. 2002;100:59–64.
Gadducci A, Cosio S, Fanucchi A, Negri S, Cristofani R, Genazzani AR. The predictive and prognostic value of serum CA 125 half-life during paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma. Gynecol Oncol. 2004;93:131–6.
Rustin GJ. The clinical value of tumour markers in the management of ovarian cancer. Ann Clin Biochem. 1996;33(Pt 4):284–9.
Meyer T, Rustin GJ. Role of tumour markers in monitoring epithelial ovarian cancer. Br J Cancer. 2000;82:1535–8.
Verheijen RH, von Mensdorff-Pouilly S, van Kamp GJ, Kenemans P. CA 125: fundamental and clinical aspects. Semin Cancer Biol. 1999;9:117–24.
Riedinger JM, Wafflart J, Ricolleau G, et al. CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol. 2006;17:1234–8.
Diaz-Montes TaB, RE. Clinical predictors of outcome in epithelial ovarian carcinoma. In: Levenback C, Sood, AK, Lu, KH, Coleman, R, editors. Prognostic and predictive factors in gynecologic cancers. Houston, TX: Informa; 2007. p. 9.
Skirnisdottir I, Sorbe B, Karlsson M, Seidal T. Prognostic importance of DNA ploidy and p53 in early stages of epithelial ovarian carcinoma. Int J Oncol. 2001;19:1295–302.
Havrilesky L, Darcy M, Hamdan H, et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2003;21:3814–25.
Rose SL. TP53/p53 as a prognostic factor. In: Levenback C, Sood AK, Lu KH, Coleman R, editors. Prognostic and predictive factors in gynecologic cancers. Houston, TX: Informa; 2007. p. 45–61.
Tothill RW, Tinker AV, George J, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008;14:5198–208.
Goff BA, Ries JA, Els LP, Coltrera MD, Gown AM. Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure. Gynecol Oncol. 1998;70:378–85.
Allan LA, Campbell MK, Milner BJ, et al. The significance of p53 mutation and over-expression in ovarian cancer prognosis. Int J Gynecol Cancer. 1996;6:483–90.
Tachibana M, Watanabe J, Matsushima Y, et al. Independence of the prognostic value of tumor suppressor protein expression in ovarian adenocarcinomas: a multivariate analysis of expression of p53, retinoblastoma, and related proteins. Int J Gynecol Cancer. 2003;13:598–606.
Dogan E, Saygili U, Tuna B, et al. p53 and mdm2 as prognostic indicators in patients with epithelial ovarian cancer: a multivariate analysis. Gynecol Oncol. 2005;97:46–52.
Geisler JP, Geisler HE, Wiemann MC, Givens SS, Zhou Z, Miller GA. Quantification of p53 in epithelial ovarian cancer. Gynecol Oncol. 1997;66:435–8.
van der Zee AG, Hollema H, Suurmeijer AJ, et al. Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. J Clin Oncol. 1995;13:70–8.
Sagarra RA, Andrade LA, Martinez EZ, Pinto GA, Syrjanen KJ, Derchain SF. P53 and Bcl-2 as prognostic predictors in epithelial ovarian cancer. Int J Gynecol Cancer. 2002;12:720–7.
Sheridan E, Silcocks P, Smith J, Hancock BW, Goyns MH. P53 mutation in a series of epithelial ovarian cancers from the U.K., and its prognostic significance. Eur J Cancer. 1994;30A:1701–4.
Mano Y, Kikuchi Y, Yamamoto K, et al. Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer. Eur J Cancer. 1999;35:1214–9.
Hashiguchi Y, Tsuda H, Inoue T, Nishimura S, Suzuki T, Kawamura N. Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients. Hum Pathol. 2004;35:165–75.
Marks JR, Davidoff AM, Kerns BJ, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res. 1991;51:2979–84.
Bali A, O’Brien PM, Edwards LS, Sutherland RL, Hacker NF, Henshall SM. Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res. 2004;10:5168–77.
Ferrandina G, Fagotti A, Salerno MG, et al. p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer. Br J Cancer. 1999;81:733–40.
Shahin MS, Hughes JH, Sood AK, Buller RE. The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma. Cancer. 2000;89:2006–17.
Baekelandt M, Kristensen GB, Nesland JM, Trope CG, Holm R. Clinical significance of apoptosis-related factors p53, Mdm2, and Bcl-2 in advanced ovarian cancer. J Clin Oncol. 1999;17:2061.
Marx D, Meden H, Ziemek T, Lenthe T, Kuhn W, Schauer A. Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer. Eur J Cancer. 1998;34:845–50.
Hartmann LC, Podratz KC, Keeney GL, et al. Prognostic significance of p53 immunostaining in epithelial ovarian cancer. J Clin Oncol. 1994;12:64–9.
Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A. Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer. 2004;14:1086–96.
Okuda T, Otsuka J, Sekizawa A, et al. p53 mutations and overexpression affect prognosis of ovarian endometrioid cancer but not clear cell cancer. Gynecol Oncol. 2003;88:318–25.
Niwa K, Itoh M, Murase T, et al. Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance. Br J Cancer. 1994;70:1191–7.
Smith-Sorensen B, Kaern J, Holm R, Dorum A, Trope C, Borresen-Dale AL. Therapy effect of either paclitaxel or cyclophosphamide combination treatment in patients with epithelial ovarian cancer and relation to TP53 gene status. Br J Cancer. 1998;78:375–81.
Leitao Jr MM, Boyd J, Hummer A, et al. Clinicopathologic analysis of early-stage sporadic ovarian carcinoma. Am J Surg Pathol. 2004;28:147–59.
Fallows S, Price J, Atkinson RJ, Johnston PG, Hickey I, Russell SE. P53 mutation does not affect prognosis in ovarian epithelial malignancies. J Pathol. 2001;194:68–75.
Schuyer M, van der Burg ME, Henzen-Logmans SC, et al. Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2. Br J Cancer. 2001;85:1359–67.
Wang Y, Helland A, Holm R, et al. TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival. Br J Cancer. 2004;90:678–85.
Wang Y, Kringen P, Kristensen GB, et al. Effect of the codon 72 polymorphism (c.215G>C, p.Arg72Pro) in combination with somatic sequence variants in the TP53 gene on survival in patients with advanced ovarian carcinoma. Hum Mutat. 2004;24:21–34.
Reles A, Wen WH, Schmider A, et al. Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer. Clin Cancer Res. 2001;7:2984–97.
Bai L, Zhu WG. p53: Structure, Function and Therapeutic Applications. J Cancer Mol. 2006;2:141–53.
Chu CS, Rubin SC. Influence of BRCA1 and BRCA2 on Ovarian Cancer Survival. In: Levenback C, Sood AK, Lu KH, Coleman R, editors. Prognostic and predictive factors in gynecologic cancers. Houston, TX: Informa; 2007. p. 15–23.
Secord AA, Lee PS, Darcy KM, et al. Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;101:390–7.
Rubin SC, Benjamin I, Behbakht K, et al. Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1. N Engl J Med. 1996;335:1413–6.
Aida H, Takakuwa K, Nagata H, et al. Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1. Clin Cancer Res. 1998;4:235–40.
Johannsson OT, Ranstam J, Borg A, Olsson H. Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J Clin Oncol. 1998;16:397–404.
Pharoah PD, Easton DF, Stockton DL, Gayther S, Ponder BA. Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. Cancer Res. 1999;59:868–71.
Boyd J, Sonoda Y, Federici MG, et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA. 2000;283:2260–5.
Zweemer RP, Verheijen RH, Coebergh JW, et al. Survival analysis in familial ovarian cancer, a case control study. Eur J Obstet Gynecol Reprod Biol. 2001;98:219–23.
Ramus SJ, Fishman A, Pharoah PD, Yarkoni S, Altaras M, Ponder BA. Ovarian cancer survival in Ashkenazi Jewish patients with BRCA1 and BRCA2 mutations. Eur J Surg Oncol. 2001;27:278–81.
Ben David Y, Chetrit A, Hirsh-Yechezkel G, et al. Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. J Clin Oncol. 2002;20:463–6.
Buller RE, Shahin MS, Geisler JP, Zogg M, De Young BR, Davis CS. Failure of BRCA1 dysfunction to alter ovarian cancer survival. Clin Cancer Res. 2002;8:1196–202.
Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer. 2003;97:2187–95.
Kringen P, Wang Y, Dumeaux V, et al. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival. BMC Cancer. 2005;5:134.
Pal T, Permuth-Wey J, Kapoor R, Cantor A, Sutphen R. Improved survival in BRCA2 carriers with ovarian cancer. Fam Cancer. 2007;6:113–9.
Banerjee S, Gore M. The future of targeted therapies in ovarian cancer. Oncologist. 2009;14:706–16.
Lose F, Nagle CM, O’Mara T, et al. Vascular endothelial growth factor gene polymorphisms and ovarian cancer survival. Gynecol Oncol. 2011;119:479–83.
Horowitz NS, Penson RT, Duda DG, et al. Safety, efficacy, and biomarker exploration in a phase II study of bevacizumab, oxaliplatin, and gemcitabine in recurrent Mullerian carcinoma. Clin Ovarian Cancer Other Gynecol Malig. 2011;4:26–33.
Sood AK, Fletcher MS, Gruman LM, et al. The paradoxical expression of maspin in ovarian carcinoma. Clin Cancer Res. 2002;8:2924–32.
Mackay HJ, Oza AM. Other new targets. Int J Gynecol Cancer. 2009;19 Suppl 2:S49–54.
Shen GH, Ghazizadeh M, Kawanami O, et al. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer. 2000;83:196–203.
Meden H, Fattahi-Meibodi A, Marx D. ELISA-based quantification of p105 (c-erbB-2, HER2/neu) in serum of ovarian carcinoma. Methods Mol Med. 2001;39:125–33.
Cheung TH, Wong YF, Chung TK, Maimonis P, Chang AM. Clinical use of serum c-erbB-2 in patients with ovarian masses. Gynecol Obstet Invest. 1999;48:133–7.
Hellstrom I, Goodman G, Pullman J, Yang Y, Hellstrom KE. Overexpression of HER-2 in ovarian carcinomas. Cancer Res. 2001;61:2420–3.
Meden H, Marx D, Raab T, Kron M, Schauer A, Kuhn W. EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer: immunohistochemical findings and prognostic value. J Obstet Gynaecol (Tokyo 1995). 1995;21:167–78.
Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37 Suppl 4:S9–15.
Elie C, Geay JF, Morcos M, et al. Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group). Br J Cancer. 2004;91:470–5.
Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR. Evaluation of monoclonal humanized anti-HER-2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER-2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003;21:283–90.
Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–43.
Lassus H, Staff S, Leminen A, Isola J, Butzow R. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma. Gynecol Oncol. 2011;120:11–7.
Bonome T, Levine DA, Shih J, et al. A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res. 2008;68:5478–86.
Mok SC, Bonome T, Vathipadiekal V, et al. A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2. Cancer Cell. 2009;16:521–32.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Oribabor, J.W., Ambrosio, A., Castro, C.M., Birrer, M.J. (2012). Ovarian Cancer. In: Bologna, M. (eds) Biotargets of Cancer in Current Clinical Practice. Current Clinical Pathology. Humana Press. https://doi.org/10.1007/978-1-61779-615-9_14
Download citation
DOI: https://doi.org/10.1007/978-1-61779-615-9_14
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-614-2
Online ISBN: 978-1-61779-615-9
eBook Packages: MedicineMedicine (R0)