Title
Author
DOI
Article Type
Special Issue
Volume
Issue
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
11st Department of Obstetrics and Gynecology of the University of Athens, School of Medicine, "Alexandra" Hospital, Greece
2Department of Clinical Therapeutics of the University of Athens, School of Medicine, "Alexandra" Hospital, Greece
3Department cif Pathology, "Alexandra" Hospital, Athens, Greece
*Corresponding Author(s): A. Protopapas E-mail:
Purpose: To evaluate the prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erbB-2 and cathepsin-D in epithelial ovarian cancer (EOC).
Methods: We analyzed 100 patients with ovarian carcinoma, FIGO Stage IC-IV who underwent primary cytoreductive surgery and received adjuvant chemotherapy with cyclophosphamide and a platinum analogue (CP) (n = 46) or paclitaxel and a platinum analogue (TP) (n = 54). Immunohistochemical expression was studied on paraffin-embedded tissue from the primary tumor.
Results: After a median follow-up of 55 months median progression-free survival (PFS) and overall survival (OS) were 16 and 41 months, respectively. Positive bcl-2 staining and absence of cathepsin-D expression were associated with an increased complete response rate in the CP group (p = 0.011 and p = 0.003) but not in the TP group. PFS and OS were not associated with the expression of any of the markers studied. FIGO stage (p = 0.006) and histology (p = 0.047) were the only independent prognostic factors for survival.
Conclusion: Bcl-2 and cathepsin D expression are associated with response to CP but not TP chemotherapy. P53, bcl-2, c-erb B-2 and cathepsin D expression was not correlated with PFS and OS in our study.
Ovarian cancer; p53; bcl-2; c-erb B-2; Cathepsins; Paclitaxel
A. Protopapas,E. Diakomanolis,A. Bamias,S. Milingos,S. Markaki,A.-M. Dimopoulos,S. Michalas. 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. European Journal of Gynaecological Oncology. 2004. 25(2);225-229.
[1] Wingo P., Tong T., Bolden S.: "Cancer statistics, 1995". CA Cancer J. Clin.. 1995, 45 (8), 8.
[2] Ozols R.F., Schwartz P.E., Eifel P.J.: "Ovarian cancer, fallopian tube and peritoneal carcinoma". In: DeVita V.T., Hellman S., Rosenberg A.S., eds. Cancer Principles and Practice of Oncology Philadelphia: Lippincott, 2001, 1597.
[3] Lowe S.W., Ruley H.E., Jacks T., Housman D.E.: "p53-dependent apoptosis modulates the cytotoxicity of anticancer agents". Cell, 1993a, 957.
[4] Gibb R.K., Taylor D.D., Wan T., O'Connor D.M., Doering D.L.. Gercel-Taylor C.: "Apoptosis as a measure to chemosensitivity to cisplatin and taxol therapy in ovarian cell lines". Gynecol. Onco/., 1997, 65, 13 (doi:I0.1006/gyno.1997-4637).
[5] Coukos G., Rubin S.: "Chemotherapy resistance in ovarian cancer new molecular perspectives". Obstet. Gynecol., 1998, 91, 783.
[6] Hesketh R.: "Apoptosis". In: The Oncogene and Tumor Supressor Gene Facts Book, 2nd edition. London, Academic Press, 1997, 34.
[7] Tilly J., Tilly K., Perez G.:'The genes of cell death and cellular susceptibility to apoptosis in the ovary: a hypothesis". Cell. Death Diff., 1997, 4, 180.
[8] Witty J.P., Jensen R.A.. Johnson A.L.: "Expression and locahzation of bcl-2 related proteins in human ovarian cancers". Anticancer Res., 1998, 18, 1223.
[9J Lowe S.W., Ruley H.E., Jacks T., Housman D.E.: "p53-dependent apoptosis modulates the cytotoxicity of anticancer agents". Cell., 1993, 74, 957.
[10] Kastan M.B., Canman C.E., Leonard C.L.: "p53, cell cycle control and apoptosis: Implications for cancer". Cancer Metastasis Rev., 1995, 14, 3.
[11] Brown R ., Clugston C., Burns P., Edlin A., Vasey P., Vojtesek B.. Kaye S.B.: "Increased accumulation of p53 protein in cisplatinresistant ovarian cell lines". Int. J. Cancer, 1993, 55, 668.
[12] Herod J.O., Eliopoulos A.G., Warwick J., Niedobitek G., Young L.S., Kerr DJ.: "The prognostic significance of bcl-2 and p53 expression in ovarian carcinoma". Cancer Res., 1996, 56, 2178.
[13] Slamon D.J., Godolphin W., Jones L.A., Holt J.A., Wong S.G., Keith D.E. et al.: "Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer". Science, 1989, 244, 707.
[14] Felip E., Del Campo J.M., Rubio D., Vidal M.T., Colomer R., Bermejo B.: "Overexpression of c-erbB-2 in epithelial ovarian cancer. Prognostic value and relationship with response to chemotherapy". Cancer, 1995, 75, 2147.
[15] Tandon A.R., Clark G.M., Chamness G.C., Chirgwin J.M., McGuire W.L.: "Cathepsin D and prognosis in breast cancer". N. Eng. J. Med., 1990, 322, 297.
[16] Scambia G., Benedetti Panici P., Ferrandina G., Salerno G., D'Agostino G., Distephano M., de Vincenzo R.: "Clinical significance of cathepsin D in primary ovarian cancer". Eur. J. Cancer, 1994, 30A, 935.
[17] Baekelandt M., Holm R., Trope C.G., Nesland J.M., Kristensen G.B.: "The significance of metastasis related factors cathepsin-D and nm23 in advanced ovarian cancer". Ann. Oneal., 1999, 10, 1335.
[18] Lavarino C., Pilotti S., Oggionni M., Gatti L., Perego P., Bresciani G., Pierotti M.A., Scambia G., Ferrandina G., Fagotti A., Mangioni C.,L ucchini V.,V ecchione F.,B olis G.,S carfone G., Zunino F.: "p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma". J. Clin. Oncol., 2000, 18, 3936.
[19] FIGO Cancer Committee: "Staging announcement". Gynecol Oncol., 1986, 25, 383.
[20] Advanced Ovarian Cancer Trialists Group: "Chemotherapy in advanced ovarian cancer: An overview of randomized clinical trials". Br. Med. J., 1991, 303, 884.
[21l Menard S.,C asalini P.,C ampiglio M., Pupa S.,A gresti R.,T aghabue E.: "HER2 overexpression in various tumor types, focussing on its relationship to the development of invasive breast cancer" Ann. Oncol., 2001, 12 (suppl. 1), S15.
[22] Henriksen R.,W ilander E.,O berg K.:" Expression and prognostic s1gnificance of bcl-2 in ovarian tumors". Br. J. Cancer, 1995, 72, 1324.
[24] Skirnisdottir I., Seidal T., Gerdin E., Sorbes B.: "The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy". Int. J. Gynecol. Cancer, 2002, 12, 265.
[24] Sagarra R. A.M., Andrade L.A.L.A., Martinez E.Z., Pinto G.A., Syrjanen K.J., Derchain S.F.M.: "p53 and bcl-2 as prognostic predictors in epithelial ovarian cancer". Int. J. Gynecol. Cancer, 2002, 12, 720.
[25] Baekelandt M., Kristensen G.B., Nesland J.M., Trope C.G., Holm R.: "Clinical significance of apoptosis-related factors p53, mdm2 and bcl-2 in ovarian tumors". J. Clin. Oncol., 1999, 17, 2061.
[26] Lotem J., Sachs L.: "Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and - defective myeloid leukemic cells". Cell. Growth & Diffe1; 1993, 4, 41.
[27] Myashita T., Reed J.C.: "Bcl-2 gene transfer increases relative resistance of S49.1 and W EH7.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs". Cancer Res., 1992, 52, 5407.
[28] Baekelandt M., Holm R., Nesland J.M., Trope C.G., Kristensen G.B.: "Expression of apoptosis-related proteins is an independent determinant of patients prognosis in advanced ovarian cancer". J Clin. Oncol., 2000, 18, 3775.
[29] Scambia G., Benedetti Panici P., Ferrandina G., Battaglia F., Baiocchi G., Mancuso S.: "Cathepsin D assay in ovarian cancer: correlation with pathological features and receptors for oestrogen. progesterone and epidermal growth factor". Br. J. Cancer, 1991, 64, 182.
[30] Wu G.S., Saftig P., Peters C., El-Deiry W.S.: "Potential role for cathepsin D in p53-dependent tumor suppression and chemosensitivity". Oncogene, 1998, 16, 2177.
[31] Rubin S.C., Finstad C.L., Wong G.Y., Almadrones L., Plante M., Lloyd K.O.: "Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: A multivariate analysis". Am. J. Obstet. Gynecol., 1993, 168, 162.
[32] Singleton T.P., Perrone T., Oakley G., Niehans G.A., Carson L., Cha S.S., Strickler J.G.: "Activation of c-erbB-2 and prognosis in ovarian carcinoma. Comparoson with histologic type, grade, and stage". Cancer, 1994, 73, 1460.
[33] Fajac A., Bernard J., Lhomme C., Rey A., Duvillard P., Rochard F., Bernaudin J.F., Riou G.: "C-erbB-2 gene amplification and protein expression in ovarian epithelial tumor、:evaluation of their respective prognostic signif、icance by multivariate analysis". Int. J Cancer, I 995, 21, 146.
[34] Cooke T., Reeves J., Lanigan A., Stanton P.: "HER2 as a prognostic and predictive marker for breast cancer". Ann. Oncol., 2001, 12 (suppl. I), S23.
Web of Science (WOS) (On Hold)
Journal Citation Reports/Science Edition
Google Scholar
JournalSeek
Top