T cell infiltration and MHC I and II expression in the presence of tumor antigens: An immunohistochemical study in patients with serous epithelial ovarian cancer

Objectives: Ovarian cancer is a frequent cause of death among women with gy naecologic malignancies despite the introduction of combination chemotherap y. There is therefore a need for new therapeutic strategies for patients wi th ovarian cancer, such as cellular immunotherapy. In this immunohistochemi cal study we analysed the expression of three tumor antigens, p53, HER-2/ne u and MUC-1 in relation to the expression of major histocompatibility compl ex (MHC) class I and II on tumor cells, and we searched for the presence of (activated) immune effector cells at the tumor site. Study design: The stu dy was carried out retrospectively in tumor tissue from 29 patients with se rous ovarian cancer. Material used had been formalin fixed and paraffin emb edded. Material had been obtained from 15 patients at staging laparotomy an d from 14 patients during second look or intervention laparotomy. Results: A positive staining for p53 was found in 19/29 (66%) of the tumors, with a high positivity in 13/29 (45%). HER-2/neu and MUC-1 staining was positive i n 8/29 (28%) and 21/28 (75%), respectively. Downregulation of MHC class I o n tumor cells was found in a minority of the patients, beta-2-microglobin ( beta (2)m) was expressed on tumor cells in all patients. High staining for CD45RO correlated with a high positive staining for granzyme-B (R=0.40, P=0 .04) and TIA-1 (R-0.39, P=0.04). A statistically significant better surviva l in the group with lower stage of disease was found. Conclusions: As only three out of 29 patients were negative for the tumor antigens p53, HER-2/ne u and MUC-1, immunotherapy aiming at all three could serve almost all patie nts with ovarian cancer. We found that granzyme-B, TIA-1 and CD45RO+ T cell s are present in the tumor biopsies, increasing this number by immunotherap y may be beneficial. The immune escape mechanism by MHC class I and beta (2 )m downregulation seems to be of minor importance. Our data support the vie w that immunotherapy may offer new possibilities with high specificity in o varian cancer (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.