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


CONCLUSIONS
Present data indicate that the intraepithelial CD3+ TIL count is a significant prognostic factor in EOC.
Fingerland Department of Pathology, Charles University, Medical School and Teaching Hospital, Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic. tomsova@fnhk.cz
Markéta
M
Tomsová
Bohuslav
B
Melichar
Iva
I
Sedláková
Ivo
I
Steiner
D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D017252:CD3 Complex / Q000276:immunology*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C495901:TP53 protein, human