Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma

Abstract

Objective: Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies in Europe and North America. Although the presence of tumor-infiltrating mononuclear cells has been documented in EOC, the association of tumor-infiltrating mononuclear cells with clinical outcome remains controversial. The aim of the present study was to investigate the prognostic significance of CD3+ tumor-infiltrating T lymphocytes (TIL) on overall survival of EOC patients.

Methods: We evaluated retrospectively by immunohistochemistry the distribution of CD3+ TIL in tumor specimens of 116 EOC patients. The expression of estrogen and progesterone receptors, Ki-67, DNA topoisomerase IIalpha, p21, p53, HER-2/neu, bax and bcl-2 was also evaluated by immunohistochemistry. The prognostic significance of CD3+ TIL and other immunohistochemical and clinical parameters was evaluated with log-rank test. Multivariate analysis was performed using the Cox regression.

Results: CD3+ TIL were observed in all tumor samples, both in cancer stroma and within cancer epithelium (intraepithelial TIL). The median counts of stromal TIL and intraepithelial TIL were 338 lymphocytes/mm2 (range 81-2094 lymphocytes/mm2) and 125 lymphocytes/mm2 (range 7-481 lymphocytes/mm2), respectively. In univariate analysis, age, stage, grade, presence of residual tumor, expression of progesterone receptors, Ki-67, DNA topoisomerase IIalpha and intraepithelial CD3+ TIL count were significant predictors of overall survival. On multivariate analysis, only the presence of residual tumor, stage, expression of progesterone receptors and intraepithelial CD3+ TIL count were found to be significant independent predictors of overall survival.

Conclusion: Present data indicate that the intraepithelial CD3+ TIL count is a significant prognostic factor in EOC.