Article Data

  • Views 191
  • Dowloads 145

Original Research

Open Access

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

  • A. Protopapas1,*,
  • E. Diakomanolis1
  • A. Bamias2
  • S. Milingos1
  • S. Markaki3
  • A.-M. Dimopoulos2
  • S. Michalas1

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

DOI: 10.12892/ejgo200402225 Vol.25,Issue 2,March 2004 pp.225-229

Published: 10 March 2004

*Corresponding Author(s): A. Protopapas E-mail:

Abstract

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.

Keywords

Ovarian cancer; p53; bcl-2; c-erb B-2; Cathepsins; Paclitaxel

Cite and Share

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.

References

[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.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top