Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.22.9739

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?  

Demir, Lutfiye (Department of Medical Oncology, Ataturk State Hospital)
Yigit, Seyran (Department of Pathology, Ataturk Training and Research Hospital, Katip Celebi University)
Sadullahoglu, Canan (Department of Pathology, Ege University)
Akyol, Murat (Department of Medical Oncology, Ataturk Training and Research Hospital, Katip Celebi University)
Cokmert, Suna (Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University)
Kucukzeybek, Yuksel (Department of Medical Oncology, Ataturk Training and Research Hospital, Katip Celebi University)
Alacacioglu, Ahmet (Department of Medical Oncology, Ataturk Training and Research Hospital, Katip Celebi University)
Cakalagaoglu, Fulya (Department of Pathology, Ataturk Training and Research Hospital, Katip Celebi University)
Tarhan, Mustafa Oktay (Department of Preventive Oncology, Institute of Oncology, Dokuz Eylul University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.22, 2014 , pp. 9739-9745 More about this Journal
Abstract
Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.
Keywords
Ovarian carcinoma; receptor expression; phenotypes; prognosis;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Boente MP, Chi DS, Hoskins WJ (1998). The role of surgery in the management of ovarian cancer: primary and interval cytoreductive surgery. Semin Oncol, 25, 326.
2 Bodnar L, Stanczak A, Cierniak S, et al (2014). Wnt/$\beta$-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer. J Ovarian Res, 7, 16.   DOI
3 Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR (2003). Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol, 21, 283-90.   DOI   ScienceOn
4 Bosmuller H, Haitchi-Petnehazy S, Webersinke G, et al (2011). Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1 expression for predicting response to platinum-based therapy. Virchows Arch, 459, 183-91.   DOI
5 Chumworathayi B (2013) Personalized cancer treatment for ovarian cancer. Asian Pac J Cancer Prev, 14, 1661-4.   과학기술학회마을   DOI   ScienceOn
6 Crawford SC, Vasey PA, Paul J, et al (2005). Does aggressive surgery only benefit patients with less advanced ovarian cancer? Results from an international comparison within the SCOTROC-1 Trial. J Clin Oncol, 23, 8802.   DOI
7 de Graeff P, Crijns AP, Ten Hoor KA, et al (2008). The ErbB signalling pathway; protein expression and prognostic value in epithelial ovarian cancer. Br J Cancer, 99, 341-9.   DOI
8 de Graeff P, Crijns AP, de Jong S, et al (2009). Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis. Br J Cancer, 101, 149-59.   DOI
9 de Toledo MC, Sarian LO, Sallum LF, et al (2013). Analysis of the contribution of immunologically-detectable HER2, steroid receptors and of the “triple-negative” tumor status to disease-free and overall survival of women with epithelial ovarian cancer. Acta Histochem, 116, 440-7.
10 Gadducci A, Zola P, Landoni F, et al (1995). Serum half-life of CA125 during early chemotherapy as an independent prognostic variable for patients with advanced epithelial ovarian cancer: results of a multicentric Italian study. Gynecol Oncol, 7, 42-7.
11 Hammond ME (2011). ASCO-CAP guidelines for breast predictive factor testing: an update. Appl Immunohistochem Mol Morphol, 19, 499-500.   DOI
12 Han Y, Huang H, Xiao Z, et al (2012). Integrated analysis of gene expression profiles associated with response of platinum/ paclitaxel-based treatment in epithelial ovarian cancer. PLoS One, 7, 52745.   DOI
13 Hogdall EV, Christensen L, Hogdall CK, et al (2007). Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from MALOVA ovarian cancer stuy. Oncol Rep, 18, 1051-9.
14 Lenhard M, Tereza L, Heublein S, et al (2012). Steroid hormone receptor expression in ovarian cancer: progesterone receptor B as prognostic marker for patients survival. BMC Cancer, 12, 553.   DOI
15 Lassus H, Leminen A, Cheng G, et al (2004). ERBB2 amplification is superior to protein expression status in predicting patient outcome in serous ovarian carcinoma. Gynecol Oncol, 92, 31-9.   DOI   ScienceOn
16 Lassus H, Sihto H, Leminen A, et al (2006). Gene amplification, mutation, and protein expression of EGFR and mutations of ERBB2 in serous ovarian carcinoma. J Mol Med, 84, 671-81.   DOI   ScienceOn
17 Lee KR, Tavassoli FA, Prat J, et al (2003). Surface epithelialstromal tumours. In: Tavassoli FA, Devilee P editors. World Health Organization classification of tumours. pathology and genetics. tumours of the breast and female genital organs. Lyon. IARC Press, 117-45.
18 Liu N, Wang X, Sheng X (2010). The clinicopathological characteristics of triple-negative epithelial ovarian cancer. J Clin Pathol, 63, 240-3.   DOI
19 Miller AB, Hoogstraten B, Staquet M, Winkler A (1981). Reporting results of cancer treatment. Cancer, 47, 207-14.   DOI   ScienceOn
20 Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A (2004). Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gyn Cancer, 14, 1086-96.   DOI
21 Noske A, Schwabe M, Weichert W, et al (2011). An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas. BMC Cancer, 11, 294.   DOI
22 Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin, 64, 9.   DOI
23 Psyrri A, Kassar M, Yu Z, et al (2005). Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res, 11, 8637-43.   DOI
24 Ray-Coquard I, Guastalla JP, Allouache D, et al (2009). HER2 Overexpression/amplification and trastuzumab treatment in advanced ovarian cancer: A GINECO Phase II Study. Clin Ovarian Cancer, 2, 17-22.   DOI
25 Saxena R, Dwivedi A (2012). ErbB family receptor inhibitors as therapeutic agents in breast cancer: current status and future clinical perspective. Med Res Rev, 32, 166-215.   DOI
26 Sinn BV, Darb-Esfahani S, Wirtz RM, et al (2011) Evaluation of a hormone receptor-positive ovarian carcinoma subtype with a favourable prognosis by determination of progesterone receptor and oestrogen receptor 1 mRNA expression in formalin-fixed paraffin-embedded tissue. Histopathol, 59, 918-27.   DOI
27 Skirnisdottir I, Sorbe B, Seidal T (2001). The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma. Int J Gyn Cancer, 11, 119-29.   DOI
28 Steffensen KD, Waldstrom M, Jeppesen U, et al (2007). The prognostic importance of cyclooxygenase 2 and HER2 expression in epithelial ovarian cancer. Int J Gynecol Cancer, 17, 798-807.   DOI
29 Suprasert P, Chalapati W. Detection of recurrence in a surveillance program for epithelial ovarian cancer. Asian Pac J Cancer Prev, 14, 7193-6.   과학기술학회마을   DOI
30 Tuefferd M, Couturier J, Penault-Llorca F, et al (2007). HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS One, 2, 1138.   DOI
31 Verri E, Guglielmini P, Puntoni M, et al (2005). HER1/ neu oncoprotein overexpression in epithelial ovarian cancer:evaluation of its prevalence and prognostic significance. Clinical study. Oncology, 68, 154-61.   DOI
32 Winter WE 3rd, Maxwell GL, Tian C, et al (2007). Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol, 25, 3621.   DOI
33 Yan B, Choo SN, Mulyadi P, et al (2011) Dual-colour HER2/ chromosome 17 chromogenic in situ hybridisation enables accurate assessment of HER2 genomic status in ovarian tumours. J Clin Pathol, 64, 1097-101.   DOI
34 Yigit S, Demir L, Tarhan MO, et al (2012). The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma. Neoplasma, 59, 475-85.   DOI
35 Young RC, Decker DG, Wharton JT, et al (1983). Staging laparotomy in early ovarian cancer. JAMA, 250, 3072.   DOI
36 Zhao D, Zhang F, Zhang W, et al (2013). Prognostic role of hormone receptors in ovarian cancer: a systematic review and meta-analysis. Int J Gyn Cancer, 23, 25-33.   DOI
37 Ziolkowska-Seta I, Madry R, Kraszewska E, et al (2009). P53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens. Gynecol Oncol, 112, 179-84.   DOI
38 Zivanovic O, Sima CS, Iasonos A, et al (2009). Exploratory analysis of serum CA-125 response to surgery and the risk of relapse in patients with FIGO stage IIIC ovarian cancer. Gynecol Oncol, 115, 209.   DOI