HER-2/neu Status and Post-Operative Survival in Epithelial Ovarian Carcinoma: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HE Yifeng ¹² ,  XU Congjian ¹ , FENG Lingda ³

1.Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China2.Center of Evidence-based Medicine, Fudan University, Shanghai 200032, China3.Shanghai First Maternity and Infant Health Hospital, Shanghai 200040, China;

Corresponding author：

XU Congjian, Email: xucj@hotmail.com

Keywords：

HER-2/neu; Epithelial ovarian carcinoma; Median survival time; 5-year survival rate; Hazard ratio

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Objective 　To use a meta-analysis method to establish quantitatively the association between the HER-2/neu gene amplification/enhanced protein expression status and the 5-year post-operative survival rate or median survival time in women with epithelial ovarian carcinoma.
Methods 　We searched and screened Chinese and English literature published since 1989 to collect all retrospective cohort studies on the prognostic significance of HER-2/neu status in this population. The survival data were analyzed using Ludwig’s centered signed rank and the DerSimonian-Laird method.
Results 　In total, 25 studies involving 3 251 patients were included. HER-2/neu was positive in 27.1% (95%CI 0 to 54.8%) of patients, which was not related to the pathological stage, type or grade of epithelial ovarian carcinoma. In HER-2/neu positive cases, the median survival time was shortened by 0.65 years, and the 5-year survival rate was lowered. The hazard ratio (HR) for mortality was 1.22 (95%C 1.09 to 1.36). By subgroup analysis, HER-2/neu protein expression was found to be most significant in prognostic assessment. Patients with a b positive value of HER-2/neu had an increased HR for the 5-year survival; and platinum-based chemotherapy was demonstrated to be less effective in HER-2/neu positive ovarian carcinoma.
Conclusion 　In gynecological oncology, it is reasonable to measure HER-2/neu as a routine pathological marker to predict a patient’s prognosis and to determine the most appropriate adjuvant chemotherapy regimen.

Citation： HE Yifeng,XU Congjian,FENG Lingda. HER-2/neu Status and Post-Operative Survival in Epithelial Ovarian Carcinoma: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2007, 07(6): 420-432. doi: Copy

1.	Liu L, Yang K. A study on C-erbB2, nm23 and p53 expressions in epithelial ovarian cancer and their clinical significance. Zhonghua Fu Chan Ke Za Zhi, 1999, 34: 101-104.
2.	Li JD, Li MD, Li YF, et al. Relationship between expressions of p53, c-erbB2 genes, proliferating cell nuclear antigen and prognosis of patients with ovarian epithelial carcinoma. Ai Zheng, 2002, 21: 292-296.
3.	Fan QB, Bian ML, Huang SZ, et al. The relation between prognosis and amplification of the c-erB-2 (HER-2/neu) proto-oncogene in ovarian carcinomas. Natl Med J China, 1994, 74: 683-685, 710.
4.	Yang H, Zhang G, Xu K, et al. c-erbB2 gene amplification in human primary epithelial ovarian cancer and its clinical significance. Zhonghua Zhongliu Zazhi, 1998, 20: 367-370.
5.	Li L, Zhong YP, Zhang W, et al. Relationship of expression of C-erbB2, C-erbB3, and C-erbB4 with ovarian carcinoma. Ai Zheng, 2004, 23: 568-572.
6.	Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 1989, 244: 707-712.
7.	Crijns APG, Boezen HM, Schouten JP, et al. Prognostic factors in ovarian cancer current evidence and future prospects. Eur J Cancer Supplements, 2005, 1: 127-145.
8.	Rubin SC, Finstad CI, Wong GY, et al. Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis. Am J Obstet Gynecol, 1993, 168: 162-169.
9.	Shih C, Padhy L, Murray M, et al. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature, 1981, 260: 261-264.
10.	Yu D, Wolf JK, Scanlon M, et al. Enhanced c-erbB-2/ neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A. Cancer Res, 1993, 53: 891-898.
11.	Fujimura M, Katsumata N, Tsuda H, et al. HER2 is frequently over-expressed in ovarian clear cell adenocarcinoma: possible novel treatment modality using recombinant monoclonal antibody against HER2, Trastuzumab. Jpn J Cancer Res, 2002, 93: 1250-1257.
12.	Berchuck A, Kamel A, Whitaker R, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res, 1990, 50: 4087-4091.
13.	Kacinski BM, Mayer AG, King BL, et al. NEU protein overexpression in benign, borderline, and malignant ovarian neoplasms. Gynecol Oncol, 1992, 44: 245-253.
14.	Scambia G, Panici PB, Ferrandina G, et al. Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer. Int J Gynaecol Cancer, 1993, 3: 271-278.
15.	Singleton TP, Perrone T, Oakley G, et al. Activation of c-erbB-2 and prognosis in ovarian carcinoma. Cancer, 1994, 73: 1460-1466.
16.	van Dam PA, Vergote IB, Lowe DG, et al. Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma. J Clin Pathol, 1994, 47: 914-919.
17.	Felip E, Del Campo JM, Rubio D, et al. Overexpression of c-erbB-2 in Epithelial Ovarian Cancer. Cancer, 1995, 75: 2147-2152.
18.	Fajac A, Benard J, Lhomme C, et al. c-erbB2 gene amplification and protein expression in ovarian epithelial tumors: evaluation of their respective prognostic significance by multivariate analysis. Int J Cancer (Pred Oncol), 1995, 64: 146-151.
19.	Medl M, Sevelda P, Czerwenka DK, et al. DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer. Gynecol Oncol, 1995, 59: 321-326.
20.	Tanner B, Kreutz E, Weikel W, et al. Prognostic significance of c-erbB-2 mRNA in ovarian carcinoma. Gynecol Oncol, 1996, 62: 268-277.
21.	Beckmann MW, An HX, Nideracher D, et al. Oncogene amplification in archival ovarian carcinoma detected by fluorescent differential polymerase chain reaction- a routine analytical approach. Int J Gynecol Cancer, 1996, 291-297.
22.	Meden H, Marx D, Roegglen T, et al. Overexpression of the oncogene c-erbB-2 (HER2/ neu) and response to chemotherapy in patients with ovarian cancer. Int J Gynecol Pathol, 1998, 17: 61-65.
23.	Hengstler JG, Lange J, Kett A, et al. Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer. Cancer res, 1999, 59: 3206-3214.
24.	Nijman HW, Kenemans P, Poort-Keesom RJJ, et al. Influence of chemotherapy on the expression of p53, HER-2/neu and proliferation markers in ovarian cancer. Eur J Obstet Gynecol Reprod Biol, 1999, 83: 201-206.
25.	Seki A, Yoshinouchi M, Seki N, et al. Detection of c-erbB-2 and FGF-3 (INT-2) gene amplification in epithelial ovarian cancer. Int J Oncol, 2000, 17: 103-106.
26.	Skirnisdottir I, Sorbe B, Seidal T. The growth factor receptor HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian cancinoma. Int J Gynecol Cancer, 2001, 11: 119-129.
27.	Hogdall EVS, Christensen L, Kjaer SK, et al. Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma. Cancer, 2003, 98: 66-73.
28.	Broet SC, Hardy-Bessard AC, Le Tourneau A, et al. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann Oncol, 2004, 15: 104-112.
29.	Nielsen JS, Jakobsen E, Holund B, et al. Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer, 2004, 14: 1086-1096.
30.	Verri E, Guglielmini P, Puntoni M, et al. NER2/ neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Oncology, 2005, 68: 154-161.
31.	Wang Y, Kristensen GB, Helland A, Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas. Am J Clin Pathol, 2005, 124: 392-401.
32.	Mayr D, Kanitz V, Amann G, et al. HER-2/neu gene amplification in ovarian tumours: a comprehensive immunohistochemical and FISH analysis on tissue microarrays. Histopathology, 2006, 48: 149-56.
33.	Haldane JS, Hird V, Hugher CM, et al. C-erbB-2 oncogene expreeion in ovarian cancer. J Pathol, 1990, 162: 231-237.
34.	Makar AP, Kristensen GB, Nesland JM, et al. The expression of c-erbB-2 (HER-2/neu) oncogene in invasive ovarian malignancies. Int J Gynecol Cancer, 1994, 4: 194-199.
35.	Rubin SC, Finstad CI, Federici MG, et al. Prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer. Cancer, 1994, 73: 1456-1459.
36.	Katsaros D, Theillet C, Zola P, et al. Concurrent abnormal expression of erbB-2, myc and ras genes is associated with poor outcome of ovarian cancer patients. Anticancer Res, 1995, 15: 1501-1510.
37.	van der Zee AGJ, Suurmeijer AJH, Krans M, 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: 70-78.
38.	Di Leo A, Biganzoli L, Bohm S, et al. An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis. Eur J Cancer, 1995, 31A: 2248-2254.
39.	Kim YT, Kim JW, Lee JW. c-erbB-2 oncoprotein assay in ovarian carcinoma and its clinical correlation with prognostic factors. Cancer Lett, 1998, 132: 91-97.
40.	Tomic S, Forko JI, Babic D, et al. c-erbB-2, p53, and nm23 proteins as prognostic factors in patients with epithelial ovarian carcinoma. Croat Med J, 2003, 44: 429-434.
41.	Hornung R, Urs E, Serenella E, et al. Analysis of potential prognostic factors in 111 patients with ovarian cancer. Cancer Lett, 2004, 206: 97-106.
42.	Protopapas A, Diakomanolis E, Bamias A, et al. The prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erb B-2 and cathepsin-D in ovarian cancer patients receiving platinum with cyclophosphamide or paclitaxel chemotherapy. Eur J Gynaecol Oncol, 2004, 25: 225-229.
43.	Chan JK, Loizzi V, Magistris A, et al. Differences in prognostic molecular markers between women over and under 45 years of age with advanced ovarian cancer. Clin Cancer Res, 2004, 10: 8538-8543.
44.	Riener EK, Arnold N, Kommoss F, et al. The prognostic and predictive value of immunohistochemically detected HER-2/neu overexpression in 361 patients with ovarian cancer: a multicenter study. Gynecol Oncol, 2004, 95: 89-94.
45.	Meden H, Marx D, Rath W, et al. Overexpression of the oncogene c-erb B2 in primary ovarian cancer: evaluation of the prognostic value in a cox proportional hazards multiple regression. Int J Gynecol Pathol, 1994, 13: 45-53.
46.	Meden H, Marx D, Raab T, et al. EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer: immunohistochemical findings and prognostic value. J Obstet Gynaecol, 1995, 21: 167-178.
47.	Leng J, Lang J, Shen K, et al. Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the ovary. Chin Med Sci J, 1997, 12: 67-70.
48.	Lassus H, Leminen A, Vayrynen A, et al. ERBB2 amplification is superior to protein expression status in predicting patient outcome in serous ovarian carcinoma. Gynecol Oncol, 2004, 92: 31-39.
49.	Tanabe H, Nishii H, Sakata A, et al. Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma. Gynecol Oncol, 2004, 94: 735-739.
50.	刘履光, 杨坤禹．C-erbB2、nm23和p53蛋白在卵巢上皮性癌中的表达及其临床意义. 中华妇产科杂志, 1999, 34: 101-104.
51.	李俊东, 李孟达, 李艳芳, 等. p53、c-erbB2基因、增殖细胞核抗原表达与卵巢上皮性癌预后的关系. 癌症, 2002, 21: 292-296.
52.	樊庆泊, 卞美璐, 黄尚志, 等. 卵巢癌原癌基因c-erbB-2扩增与预后的关系. 中华医学杂志, 1994, 74: 683-685, 710.
53.	杨慧娟, 张国玲, 许凯黎, 等. 原发性上皮性卵巢癌组织中c-erbB2基因扩增及其临床意义. 中华肿瘤杂志, 1998, 20: 367-370．.
54.	李力, 钟艳萍, 张玮, 等. C-erbB2、C-erbB3、C-erbB4的表达与卵巢恶性肿瘤的关系. 癌症, 2004, 23: 568-572.
55.	Ellis IO, Bartlett J, Dowsett M, et al. Updated recommendations for HER2 testing in the UK. J Clin Pathol, 2004, 57: 233-237.
56.	Menard S, Balsari A, Casalini P, et al. HER-2-positive Breast Carcinomas As a Particular Subset with Peculiar Clinical Behaviors. Clin Cancer Res, 2002, 8: 520-525.
57.	Hogberg T, Glimelius B, Nygren P. A Systematic Overview of Chemotherapy Effects in Ovarian Cancer. Acta Oncologica, 2001, 40: 340-360.
58.	Ross JS, Fletcher JA, Linette GP, et al. The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist, 2003, 8: 307-325.
59.	Barrett-Lee. Growth factor signalling in clinical breast cancer and its impact on response to conventional therapies: a review of chemotherapy. Endocrine-Related Cancer, 2005, 12: S125-S133.

1. Liu L, Yang K. A study on C-erbB2, nm23 and p53 expressions in epithelial ovarian cancer and their clinical significance. Zhonghua Fu Chan Ke Za Zhi, 1999, 34: 101-104.
2. Li JD, Li MD, Li YF, et al. Relationship between expressions of p53, c-erbB2 genes, proliferating cell nuclear antigen and prognosis of patients with ovarian epithelial carcinoma. Ai Zheng, 2002, 21: 292-296.
3. Fan QB, Bian ML, Huang SZ, et al. The relation between prognosis and amplification of the c-erB-2 (HER-2/neu) proto-oncogene in ovarian carcinomas. Natl Med J China, 1994, 74: 683-685, 710.
4. Yang H, Zhang G, Xu K, et al. c-erbB2 gene amplification in human primary epithelial ovarian cancer and its clinical significance. Zhonghua Zhongliu Zazhi, 1998, 20: 367-370.
5. Li L, Zhong YP, Zhang W, et al. Relationship of expression of C-erbB2, C-erbB3, and C-erbB4 with ovarian carcinoma. Ai Zheng, 2004, 23: 568-572.
6. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 1989, 244: 707-712.
7. Crijns APG, Boezen HM, Schouten JP, et al. Prognostic factors in ovarian cancer current evidence and future prospects. Eur J Cancer Supplements, 2005, 1: 127-145.
8. Rubin SC, Finstad CI, Wong GY, et al. Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis. Am J Obstet Gynecol, 1993, 168: 162-169.
9. Shih C, Padhy L, Murray M, et al. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature, 1981, 260: 261-264.
10. Yu D, Wolf JK, Scanlon M, et al. Enhanced c-erbB-2/ neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A. Cancer Res, 1993, 53: 891-898.
11. Fujimura M, Katsumata N, Tsuda H, et al. HER2 is frequently over-expressed in ovarian clear cell adenocarcinoma: possible novel treatment modality using recombinant monoclonal antibody against HER2, Trastuzumab. Jpn J Cancer Res, 2002, 93: 1250-1257.
12. Berchuck A, Kamel A, Whitaker R, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res, 1990, 50: 4087-4091.
13. Kacinski BM, Mayer AG, King BL, et al. NEU protein overexpression in benign, borderline, and malignant ovarian neoplasms. Gynecol Oncol, 1992, 44: 245-253.
14. Scambia G, Panici PB, Ferrandina G, et al. Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer. Int J Gynaecol Cancer, 1993, 3: 271-278.
15. Singleton TP, Perrone T, Oakley G, et al. Activation of c-erbB-2 and prognosis in ovarian carcinoma. Cancer, 1994, 73: 1460-1466.
16. van Dam PA, Vergote IB, Lowe DG, et al. Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma. J Clin Pathol, 1994, 47: 914-919.
17. Felip E, Del Campo JM, Rubio D, et al. Overexpression of c-erbB-2 in Epithelial Ovarian Cancer. Cancer, 1995, 75: 2147-2152.
18. Fajac A, Benard J, Lhomme C, et al. c-erbB2 gene amplification and protein expression in ovarian epithelial tumors: evaluation of their respective prognostic significance by multivariate analysis. Int J Cancer (Pred Oncol), 1995, 64: 146-151.
19. Medl M, Sevelda P, Czerwenka DK, et al. DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer. Gynecol Oncol, 1995, 59: 321-326.
20. Tanner B, Kreutz E, Weikel W, et al. Prognostic significance of c-erbB-2 mRNA in ovarian carcinoma. Gynecol Oncol, 1996, 62: 268-277.
21. Beckmann MW, An HX, Nideracher D, et al. Oncogene amplification in archival ovarian carcinoma detected by fluorescent differential polymerase chain reaction- a routine analytical approach. Int J Gynecol Cancer, 1996, 291-297.
22. Meden H, Marx D, Roegglen T, et al. Overexpression of the oncogene c-erbB-2 (HER2/ neu) and response to chemotherapy in patients with ovarian cancer. Int J Gynecol Pathol, 1998, 17: 61-65.
23. Hengstler JG, Lange J, Kett A, et al. Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer. Cancer res, 1999, 59: 3206-3214.
24. Nijman HW, Kenemans P, Poort-Keesom RJJ, et al. Influence of chemotherapy on the expression of p53, HER-2/neu and proliferation markers in ovarian cancer. Eur J Obstet Gynecol Reprod Biol, 1999, 83: 201-206.
25. Seki A, Yoshinouchi M, Seki N, et al. Detection of c-erbB-2 and FGF-3 (INT-2) gene amplification in epithelial ovarian cancer. Int J Oncol, 2000, 17: 103-106.
26. Skirnisdottir I, Sorbe B, Seidal T. The growth factor receptor HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian cancinoma. Int J Gynecol Cancer, 2001, 11: 119-129.
27. Hogdall EVS, Christensen L, Kjaer SK, et al. Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma. Cancer, 2003, 98: 66-73.
28. Broet SC, Hardy-Bessard AC, Le Tourneau A, et al. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann Oncol, 2004, 15: 104-112.
29. Nielsen JS, Jakobsen E, Holund B, et al. Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer, 2004, 14: 1086-1096.
30. Verri E, Guglielmini P, Puntoni M, et al. NER2/ neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Oncology, 2005, 68: 154-161.
31. Wang Y, Kristensen GB, Helland A, Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas. Am J Clin Pathol, 2005, 124: 392-401.
32. Mayr D, Kanitz V, Amann G, et al. HER-2/neu gene amplification in ovarian tumours: a comprehensive immunohistochemical and FISH analysis on tissue microarrays. Histopathology, 2006, 48: 149-56.
33. Haldane JS, Hird V, Hugher CM, et al. C-erbB-2 oncogene expreeion in ovarian cancer. J Pathol, 1990, 162: 231-237.
34. Makar AP, Kristensen GB, Nesland JM, et al. The expression of c-erbB-2 (HER-2/neu) oncogene in invasive ovarian malignancies. Int J Gynecol Cancer, 1994, 4: 194-199.
35. Rubin SC, Finstad CI, Federici MG, et al. Prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer. Cancer, 1994, 73: 1456-1459.
36. Katsaros D, Theillet C, Zola P, et al. Concurrent abnormal expression of erbB-2, myc and ras genes is associated with poor outcome of ovarian cancer patients. Anticancer Res, 1995, 15: 1501-1510.
37. van der Zee AGJ, Suurmeijer AJH, Krans M, 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: 70-78.
38. Di Leo A, Biganzoli L, Bohm S, et al. An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis. Eur J Cancer, 1995, 31A: 2248-2254.
39. Kim YT, Kim JW, Lee JW. c-erbB-2 oncoprotein assay in ovarian carcinoma and its clinical correlation with prognostic factors. Cancer Lett, 1998, 132: 91-97.
40. Tomic S, Forko JI, Babic D, et al. c-erbB-2, p53, and nm23 proteins as prognostic factors in patients with epithelial ovarian carcinoma. Croat Med J, 2003, 44: 429-434.
41. Hornung R, Urs E, Serenella E, et al. Analysis of potential prognostic factors in 111 patients with ovarian cancer. Cancer Lett, 2004, 206: 97-106.
42. Protopapas A, Diakomanolis E, Bamias A, et al. The prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erb B-2 and cathepsin-D in ovarian cancer patients receiving platinum with cyclophosphamide or paclitaxel chemotherapy. Eur J Gynaecol Oncol, 2004, 25: 225-229.
43. Chan JK, Loizzi V, Magistris A, et al. Differences in prognostic molecular markers between women over and under 45 years of age with advanced ovarian cancer. Clin Cancer Res, 2004, 10: 8538-8543.
44. Riener EK, Arnold N, Kommoss F, et al. The prognostic and predictive value of immunohistochemically detected HER-2/neu overexpression in 361 patients with ovarian cancer: a multicenter study. Gynecol Oncol, 2004, 95: 89-94.
45. Meden H, Marx D, Rath W, et al. Overexpression of the oncogene c-erb B2 in primary ovarian cancer: evaluation of the prognostic value in a cox proportional hazards multiple regression. Int J Gynecol Pathol, 1994, 13: 45-53.
46. Meden H, Marx D, Raab T, et al. EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer: immunohistochemical findings and prognostic value. J Obstet Gynaecol, 1995, 21: 167-178.
47. Leng J, Lang J, Shen K, et al. Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the ovary. Chin Med Sci J, 1997, 12: 67-70.
48. Lassus H, Leminen A, Vayrynen A, et al. ERBB2 amplification is superior to protein expression status in predicting patient outcome in serous ovarian carcinoma. Gynecol Oncol, 2004, 92: 31-39.
49. Tanabe H, Nishii H, Sakata A, et al. Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma. Gynecol Oncol, 2004, 94: 735-739.
50. 刘履光, 杨坤禹．C-erbB2、nm23和p53蛋白在卵巢上皮性癌中的表达及其临床意义. 中华妇产科杂志, 1999, 34: 101-104.
51. 李俊东, 李孟达, 李艳芳, 等. p53、c-erbB2基因、增殖细胞核抗原表达与卵巢上皮性癌预后的关系. 癌症, 2002, 21: 292-296.
52. 樊庆泊, 卞美璐, 黄尚志, 等. 卵巢癌原癌基因c-erbB-2扩增与预后的关系. 中华医学杂志, 1994, 74: 683-685, 710.
53. 杨慧娟, 张国玲, 许凯黎, 等. 原发性上皮性卵巢癌组织中c-erbB2基因扩增及其临床意义. 中华肿瘤杂志, 1998, 20: 367-370．.
54. 李力, 钟艳萍, 张玮, 等. C-erbB2、C-erbB3、C-erbB4的表达与卵巢恶性肿瘤的关系. 癌症, 2004, 23: 568-572.
55. Ellis IO, Bartlett J, Dowsett M, et al. Updated recommendations for HER2 testing in the UK. J Clin Pathol, 2004, 57: 233-237.
56. Menard S, Balsari A, Casalini P, et al. HER-2-positive Breast Carcinomas As a Particular Subset with Peculiar Clinical Behaviors. Clin Cancer Res, 2002, 8: 520-525.
57. Hogberg T, Glimelius B, Nygren P. A Systematic Overview of Chemotherapy Effects in Ovarian Cancer. Acta Oncologica, 2001, 40: 340-360.
58. Ross JS, Fletcher JA, Linette GP, et al. The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist, 2003, 8: 307-325.
59. Barrett-Lee. Growth factor signalling in clinical breast cancer and its impact on response to conventional therapies: a review of chemotherapy. Endocrine-Related Cancer, 2005, 12: S125-S133.

Chinese Journal of Evidence-Based Medicine

HER-2/neu Status and Post-Operative Survival in Epithelial Ovarian Carcinoma: A Meta-analysis

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