• 1. 復旦大學附屬婦產(chǎn)科醫(yī)院(上海 200011)2. 復旦大學循證醫(yī)學中心(上海200032)3. 上海第一婦嬰保健院(上海 200040);

目的  以Meta分析的方法定量評估HER-2/neu基因擴增/或表達增強狀態(tài)與上皮性卵巢癌患者手術(shù)后的中位生存期和5年生存率的關(guān)聯(lián)性。
方法  檢索、篩選1989年以來所有論述HER-2/neu狀態(tài)與患者預后關(guān)系的中、英文回顧性研究文獻。在Ludwig中心符號軼(Centered signed rank)和DerSimonian-Laird等方法基礎上對各研究提供的生存數(shù)據(jù)進行統(tǒng)計分析。
結(jié)果  共納入25篇文獻,3 251例患者。HER-2/neu表達率為27.1%[95%CI(0,54.8%)],與病理分期、分型和分級無關(guān)。HER-2/neu陽性者中位生存期平均減少0.65年,5年生存率下降[HR=1.22,95%CI(1.09,1.36)]。亞組分析顯示,HER-2/neu蛋白表達與預后關(guān)系最明確,強陽性者5年內(nèi)死亡風險增加,且對鉑類化療藥物的反應性減低。
結(jié)論  在婦科腫瘤臨床中,將HER-2/neu作為常規(guī)的病理指標使用,有助于進行合理的預后評估,并制定個體化化療方案。

引用本文: 何以豐,徐叢劍,馮令達. HER-2/neu與上皮性卵巢癌術(shù)后生存率相關(guān)性的Meta分析. 中國循證醫(yī)學雜志, 2007, 07(6): 420-432. doi: 復制

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. 劉履光, 楊坤禹.C-erbB2、nm23和p53蛋白在卵巢上皮性癌中的表達及其臨床意義. 中華婦產(chǎn)科雜志, 1999, 34: 101-104.
51. 李俊東, 李孟達, 李艷芳, 等. p53、c-erbB2基因、增殖細胞核抗原表達與卵巢上皮性癌預后的關(guān)系. 癌癥, 2002, 21: 292-296.
52. 樊慶泊, 卞美璐, 黃尚志, 等. 卵巢癌原癌基因c-erbB-2擴增與預后的關(guān)系. 中華醫(yī)學雜志, 1994, 74: 683-685, 710.
53. 楊慧娟, 張國玲, 許凱黎, 等. 原發(fā)性上皮性卵巢癌組織中c-erbB2基因擴增及其臨床意義. 中華腫瘤雜志, 1998, 20: 367-370..
54. 李力, 鐘艷萍, 張瑋, 等. C-erbB2、C-erbB3、C-erbB4的表達與卵巢惡性腫瘤的關(guān)系. 癌癥, 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 33. Haldane JS, Hird V, Hugher CM, et al. C-erbB-2 oncogene expreeion in ovarian cancer. J Pathol, 1990, 162: 231-237.
  34. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 50. 劉履光, 楊坤禹.C-erbB2、nm23和p53蛋白在卵巢上皮性癌中的表達及其臨床意義. 中華婦產(chǎn)科雜志, 1999, 34: 101-104.
  51. 51. 李俊東, 李孟達, 李艷芳, 等. p53、c-erbB2基因、增殖細胞核抗原表達與卵巢上皮性癌預后的關(guān)系. 癌癥, 2002, 21: 292-296.
  52. 52. 樊慶泊, 卞美璐, 黃尚志, 等. 卵巢癌原癌基因c-erbB-2擴增與預后的關(guān)系. 中華醫(yī)學雜志, 1994, 74: 683-685, 710.
  53. 53. 楊慧娟, 張國玲, 許凱黎, 等. 原發(fā)性上皮性卵巢癌組織中c-erbB2基因擴增及其臨床意義. 中華腫瘤雜志, 1998, 20: 367-370..
  54. 54. 李力, 鐘艷萍, 張瑋, 等. C-erbB2、C-erbB3、C-erbB4的表達與卵巢惡性腫瘤的關(guān)系. 癌癥, 2004, 23: 568-572.
  55. 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. 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. 57. Hogberg T, Glimelius B, Nygren P. A Systematic Overview of Chemotherapy Effects in Ovarian Cancer. Acta Oncologica, 2001, 40: 340-360.
  58. 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. 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.