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Original Research

Open Access

Multivariate analysis by Cox proportional hazard model on prognosis of patient with epithelial ovarian cancer

  • M. Wang1,*,
  • Y. He1
  • L. Shi1
  • C. Shi1

1Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Heping Shenyang, China

DOI: 10.12892/ejgo201102171 Vol.32,Issue 2,March 2011 pp.171-177

Published: 10 March 2011

*Corresponding Author(s): M. Wang E-mail: wm21st@hotmail.com

Abstract

Purpose of investigation: To evaluate the influence of various clinicopathological and biochemical factors on the survival of patients with epithelial ovarian cancer (EOC) after radical resection. Methods: A retrospective analysis was made for 183 cases of epithelial ovarian cancer treated from January 1997 to January 2001. Six clinicopathological factors, including menopause, histological type, histological grade, lymph node metastasis, FIGO stage and chemotherapy that could possibly influence survival were selected. The expression of COX-2 and VEGF protein as two biochemical factors were detected in EOC tissues using immunohistochemical staining. Independent variables were first analyzed by univariate methods. A multivariate analysis of these variables was performed using the Cox proportional hazard regression model. Results: The ovarian cumulative survival rate was 48.71% for three years and 30.71% for five years. Univariate analysis of overall survival involving all the patients indentified five factors that were associated with a significant outcome: menopause, histological grade, FIGO stage, COX-2 or VEGF expression level (p < 0.05). The expression of COX-2 was positive in 140 (76.5%) of these 183 cases, but was not associated with menopause, histological type, histological grade, lymph node metastasis or FIGO stage. Median survival time was 24.56 months for the patients with COX-2 positive expression, and 47.52 months for those with COX-2 negative expression (p < 0.05). VEGF protein overexpression was examined in 117 (63.93%) of all 183 cases, and was associated with lymph node metastasis (p <0.05), but not associated with menopause, histological grade, histological type or FIGO stage. The median survival time was 23.36 months for the patients with VEGF detected expression, and 42.09 months for those with no VEGF detected expression (p < 0.05). When the interactive effects of these factors were taken into account, COX-2 expression, FIGO stage, VEGF expression and histological grade were the four most important prognostic factors by multivariate analysis using the Cox proportional hazards model. Risk of death for the patients with COX-2 positive expression was 2.8 times than that with COX-2 negative expression, and for FIGO stage, VEGF expression and histological grade, risk of death was 2.2, 2.1, and 1.84 times, respectively. Conclusion: COX-2 expression, FIGO stage, VEGF expression and histological grade are the most important prognostic factors for EOC after curative resection.

Keywords

Ovarian cancer; Clinical pathological factors; COX-2; VEGF; Prognosis; Cox’s proportional hazard regression model

Cite and Share

M. Wang,Y. He,L. Shi,C. Shi. Multivariate analysis by Cox proportional hazard model on prognosis of patient with epithelial ovarian cancer. European Journal of Gynaecological Oncology. 2011. 32(2);171-177.

References

[1] Dannenberg A.J., Altorki N.K., Boyle J.O., Dang C., Howe L.R., Weksler B.B., Subbaramaiah K.: “Cyclo-oxygase 2: a pharmacological target for the prevention of cancer”. Lancet Oncol., 2001, 2, 544.

[2] Saklesa E.: “Prognostic markers in epithelial ovarian cancer”. Int. J. Gynecol. Pathol., 1993, 12, 156.

[3] Bauknecht T., Runge M., Schwall M., Pfleiderer A.: “Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas”. Gynecol. Oncol., 1988, 2, 147.

[4] Rajkumar T., Gooden C.S.R., Lemoine N.R., Gullick W.J., Goden

C. S.: “Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RT”. J. Pathol., 1993, 170, 271.

[5] Zheng H.: “The biochemical prognosis factors of epithelial ovarian cancer”. Obstet. Gynecol., 2004 31, 37.

[6] Soslow R.A., Dannenberg A.J., Rush D. et al.: “COX-2 is expressed in human pulmonary, colonic, and mammary tumors”. Cancer, 2000, 89, 2637.

[7] Davies G., Salter J., Hills M., Martin L.A., Sacks N., Dowsett M.: “Correlation between cyclooxygenase-2 expression and angiogenes is in human breast cancer”. Clin. Cancer Res., 2003, 9, 2651.

[8] Zhi Y.H., Liu R.S., Song M.M., Tian Y., Long J., Tu W., Guo R.X.: “Cyclo-oxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma”. World J. Gastroenterol., 2005, 11, 3724.

[9] Sheng H., Shao J., Morrow J.D., Beauchamp R.D., DuBios R.N.: “Modulation of apoptosis and bcl-2 expression by prostaglandin E2 in human colon cancer cells”. Cancer Res., 1998, 58, 362.

[10] Huang M., Stolina M., Sharma S., Mao J.T., Zhu L., Miller P.W. et al.: “Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: upregulation of interleukin 10 and down-regulation of interleukin 12 production”. Cancer Res., 1998, 58, 1208.

[11] Inoue H., Yokoyaya C., Hara S., Tone Y., Tanabe T.: “Transcriptional regulation of human prostaglandin-endoperoxide synthase-2 gene by lipopoly-saccharide and phordol ester in vascular enlothelial cells”. J. Biol. Chem., 1995, 270, 24965.

[12] Trifan O.C., Hla T.: “Cyclo-oxygenase-2 modulates cellular growth and promotes tumorigenesis”. J. Cell. Mol. Med., 2003, 7, 207.

[13] Gupta S., Srivastava M., Ahmad N., Bostwick D.G., Mukhtar H.: “Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma”. Prostate, 2000, 42, 73.

[14] Lee J.S., Choi Y.D., Lee J.H., Nam J.H., Choi C., Lee M.C. et al.: “Expression of cyclooxygenase-2 in epithelial ovarian tumors and its relation to vascular endothelial growth factor and p53 expression”. Int. J. Gynecol. Cancer, 2006, 16 (suppl. 1), 247.

[15] Land H., Parada L.F., Weinberg R.A.: “Tumorigenic conversion of primary embryo fibroblasts reguires at least two cooperating onco-genes”. Nature, 1983, 304, 596.

[16] Slamon D.J., Dekernion J.B., Verma I.M., Cline M.J.: “Expression of cellular oncogenes in human malignancies”. Science, 1984, 224, 256.

[17] Siironen P., Ristimaki A., Narko K., Nordling S., Louhimo J., Andersson S. et al.: “VEGF-C and COX-2 expression in papillary thyroid cancer”. Endocr. Relat. Cancer, 2006, 13, 465.

[18] Fujimoto J., Toyoki H., Sakaguchi H., Jahan I., Alam S.M., Tamaya T.: “Clinical implications of expression of cyclo-oxygenase-2 related to angiogenesis in ovarian cancer”. Oncol. Rep., 2006, 15, 21.

[19] Nishida N., Yano H., Komai K., Nishida T., Kamura T., Kojiro M.: “Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma”. Cancer, 2004, 101, 1364.

[20] Tang J., Cai S.M., Zhang R.Y., Wang H.Y.: “The significance of abdominal residue after primary cytoreductive surgery for Stage III ovarian cancer”. China Oncol., 2004, 14, 31.

[21] Zhang X.Y.: “Practical Obstetrics & Gynecology”. Edition 2, Beijing, People’s Medical Publishing House, 2004,·686.

[22] Cox D.R.: “Regression models and life table”. JR Statist. Soc. Ser B., 1972, 34, 187.

[23] Luo F.T., Hu M.X.: “The role of Cox proportional in the analysis of cancer prognosis factors”. Cancer, 1991, 10, 84.

[24] Gao X.Z., Xu S.X.: “Current cancer diagnosis and treatment”. Beijing Scientific and Technological Literature Publishing House, 1997, 323.

[25] Raspollini M.R., Amunni G., Villanucci A., Baroni G., Boddi V., Taddei G.L.: “Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma”. Int. J. Gynecol. Cancer, 2004, 14, 815.

[26] Scorilas A., Borgono C.A., Harbeck N., Dom J., Schmaifedt B., Schmitt M., Diamandis E.P.: “Human kallikrein 13 protein in ovarian cancer cytosols: a newfavorable prognostic marker”. J. Clin. Oncol., 2004, 22, 678.

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