Multidrug resistance gene- I (Pgp) expression in epithelial ovarian malignancies

Objective: To assess the value of P-glycoprotein (Pgp) expression in advanced epithelial ovarian cancer with regard to clinicopathological findings and disease prognosis.

Methods: Twenty-four cases diagnosed as primary epithelial ovarian malignancies, between 1993-1999, were enrolled in this study. All of the cases had undergone cytoreductive surgery and an optimal staging procedure. Following cytoreductive surgery, in 18 patients, cisplatin+cyclophosphamide, and in six patients, cisplatin+paclitaxel combination chemotherapy regimens were initiated. After six courses of chemotherapy, cases were evaluated by pelvic examination, transvaginal ultrasound, pelvi-abdominal tomography and serum Ca-125 levels for the presence of residual disease. Following this evaluation residual tumor was detected in 14 cases and secondary cytoreductive surgery was undergone. In ten cases without any clinical and laboratory confirmation of the presence of tumor, second-look laparotomy was performed. In 24 epithelial ovarian cancer cases, both in primary or secondary cytoreductive surgery, Pgp expression was determined by immunohistochemical methods.

Results: Following primary surgery, in 25% (6/24) of cases, analysis of tumor specimens showed presence of Pgp expression. In cases recurring after first-line chemotherapy, Pgp expression was not statistically different in regard to chemotherapy regimen (p = 0.098). Pgp expression in tumoral tissues after chemotherapy did show a higher Pgp expression than before chemotherapy (p = 0.016). No significant correlation was relevant between Pgp expression and Ca-125 levels, histopathological differentiation, histologic subgroups of tumor, primary and residual tumor sizes and overall survival.

Conclusion: In epithelial ovarian cancer, Pgp expression has no effect on overall disease survival.

P-glycoprotein; Multidrug resistance; Epithelial ovarian cancer

[1] Wingo P. A., Tong T., Bolden S.: "Cancer statistics CA". Cancer J. Clin., 1995, 45, 8.

[2] Fojo A.. Hamilton T. C., Young R. C., Ozols R. F.: "Multidrug resistance in ovarian cancer". Cancer, 1987, 60 (8 suppl), 2075.

[3] Kubota N., Nishio K., Takeda Y. et al.: "Chraracterisation of an etoposide resistant human ovarian cancer cell line". Cancer Chemother. Phannacol., 1994, 34, 183.

[4] Gupta R. S.: "Cross resistance of vinblastine and taxol resistant mutants of chinese hamster ovary cells to other anticancer drugs". Cancer Treat. Rep., 1985, 69, 515.

[5] Beck W. T., Dalton W. S.: "Mechanisms of drug resistance". De Vita V. T., Helman S., Rosenborg S. A. (eds): Cancer Principles and Practice of Oncology, Raven-Lippincott, Philadelphia 1998, 498.

[6] Leighton J. C.,G oldstein L. J.: "P-glycoprotein in adult solid tumors: expression and prognostic significance". Hematology Oncology Clin. North Am., 1995, 9, 251.

[7] Sekiyas S., Nunoyama T., Skirasawaka H., Kimura H., Kawata M., lijima N. et al.: "Expression of human multidrug resistance gene in human ovarian cancer cell lines". Arch. Gynecol. Obstet., 1992, 251 (2), 79.

[8] Beck W. T.,G roga,T . M.,W ilman C. I.,C ordon-Cardo C., Parham D. M., Kuttesch J. F. et al.: "Methods to detect P-glycoproteinassociated multidrug resistance in patients'tumors: concensus recommendations". Cancer Res., 1996, 56 (3), 3010.

[9] Van der Heyden S.,G hevens E.,B ruijn E. D.: "P-glycoprotein: clinical significance and methods of analysis“ Critical Rev. Clin. Lab. Sciences,1995, 32 (3), 221.

[10] Borst P., Schinkel S. H.: "What we have learnt thus from mice with disrupted p-glycoprotein genes?". Eur. J. Cancer, 1990, 32(A), 985.

[11] Van der Zee A.G. J., Hollema H., Suurmeijer A. J. H.: "Value of p-glycoprotein, glythathione S transferase cErb-B2 and p53 as prognostic factors in ovarian carcinoma". J. Clin. Oneal., 1995, 13, 70.

[12] Goldstein L. J.,G alski H.,F ojo A. et al.: "Expression of a resistance gene in human cancers". J. Natl. Cancer Inst., 1989, 81, 116.

[13] Schneider J., Centeno M., Jimenez E. et al.: "Correlation of MORI expression an oncogenic activation in human epithelial ovarian carcinoma". Anticancer Res., 1997, 17, 2147.

[14] Kodama J., Hayase R., Yoshinouchi M., Okuda H., Kudo T.: "Immunohistochemical analysis of P-glycoprotein expression in diverse histological types of epithelial ovarian tumors". Acta Med. Okayama, 1994, 48 (5), 249.

[15] Arao S., Suwa H., Mandai M.: "Expression of multidrug resistant gene and localisation of P-glycoprotein in human primary ovarian cancer". Cancer Res., 1994, 45, 1355.

[16] Baekelandt M. M., Holm R., Nesland J. M., Trope C. G., Kristensen G. B.: "P-glycoprotein expression in a marker for chemotherapy resistance and prognosis in advanced ovarian cancer". Anticancer Res., 2000, 20 (2B), 1061.

[17] Holzmayer T. A., Hilsenbeck S., Hoff、D. D. et al.: "Clinical correlates of MDR 1 (P glycoprotein) gene expression in ovarian and small cell lung carcinomas". J. Natl. Cancer Inst., 1992, 84, 1486.

[18] Scheffer G. L., Kool M., Heijn M., de Haas M., Pijnenborg A. C., Wijnenbolds J. et al.: "Specific detection of multidrug resistance proteins MRPI, MRP2, MRP5 and MDR3 P-glycoprotein with a panel of panel of monoclonal antibodies". Cancer Res., 2000, 60(18), 526.

[19] Chen G. K., Duran G. E., Mangili A., Beketic-Oreskovic L., Sikic B. I.: "MDR-1 activation is the predominant resistance mechanism selected by vinblastine in MES-SA cells". B,: J. Cancer, 2000, 83(7), 892.

[20] Fracasso P. M.: "Overcoming drug resistance m ovarian carcinoma". Curr. Oncol. Rep., 2001, 3 (1), 19.