Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma
Introduction
Epithelial ovarian cancer (EOC) is the fifth most common malignancy in women and ranks fourth in cancer mortality in the Western world [1]. Among the gynecological malignancies, EOC is the most common cause of death. The average 5-year survival is around 40%, and in patients with advanced disease only 10–20% [1], [2].
In the early 1990s, studies performed by the Gynecologic Oncology Group (GOG) demonstrated that age, performance status, stage, tumor grade, tumor cell type (histology), presence or absence of ascites, size and number of residual lesions after primary cytoreduction surgery and administration of cisplatin-based chemotherapy are of prognostic significance in advanced EOC [3], [4], [5]. Prognostic significance was also investigated for expression of molecular targets, including estrogen and progesterone receptors, Ki-67, DNA topoisomerase IIα, p21, p53, HER-2/neu, bax and bcl-2 [6].
In recent years, considerable progress has been made in understanding the role of the immune system in tumor progression [7], [8]. The presence of tumor-infiltrating mononuclear cells consisting of T lymphocytes (helper and suppressor/cytotoxic), natural killer cells, B lymphocytes and macrophages indicates an active immune response of the host that is possibly directed against the tumor antigens. Most of the infiltrating T cells are CD8+ lymphocytes that could mediate specific cytotoxicity against tumor cells. On the other hand, macrophages (CD68+ cells) are the most prevalent population of the tumor-infiltrating mononuclear cells. The primary role of tumor-infiltrating macrophages could consist in recruitment and activation of lymphocytes through the presentation of tumor antigens. Nevertheless, the functional heterogeneity of macrophages may result in antagonistic functions, and they can both inhibit and stimulate the proliferation of tumor cells [9]. The presence of tumor-infiltrating T lymphocytes (TIL) has been reported to correlate with better prognosis in different primary tumors, but conflicting results have been published regarding the prognostic significance of TIL in EOC [10], [11].
In the present study, we analyzed the impact of CD3+ TIL and some other immunohistochemical parameters, including estrogen and progesterone receptors, Ki-67, DNA topoisomerase IIα, p21, p53, HER-2/neu, bax and bcl-2 on overall survival of patients with EOC.
Section snippets
Patients
We retrospectively evaluated tissue blocks of 116 consecutive EOC patients who underwent primary surgery between January 1996 and December 2003 at two hospitals in Hradec Králové. The surgical specimens from these two hospitals are sent for histological evaluation exclusively to Fingerland Department of Pathology. The patients underwent a laparotomy for tumor debulking with abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy and omentectomy with examination of the serosal
Results
The clinical and histological characteristics of the patients included in the present study are summarized in Table 1. The median age of the study population was 53 years (range 27–82, mean 55 years). The majority of patients presented with serous histology (47%), stage III (63%) and grade 2 (46%) or 3 (41%). Of the 116 patients examined, 62 (53%) were dead before the end of the observation period. The median duration of follow-up for the entire group was 39 months (range 1–120 months). The
Discussion
Present data demonstrate that the presence of intraepithelial TIL correlates with outcome in EOC. Among other histological or immunohistochemical parameters investigated in the present study, only the expression of progesterone receptor was an independent prognostic indicator in multivariate analysis. The host–tumor interactions play an important role in tumor progression [9], and the presence of TIL within the tumor microenvironment may be considered to represent an indicator of the host
Acknowledgment
The project was supported by the grant of the Czech Ministry of Health NR8363-3/2005.
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