Immunologic Heterogeneity and Survival in Metastatic Serous Ovarian Carcinoma.
Ian S Hagemann, Priya Patel, Andrea R Hagemann, Li-Ping Wang, George Coukos, Michael D Feldman. Univ of Pennsylvania, Philadelphia
Background: The presence of tumor-infiltrating lymphocytes (TILs) in epithelial ovarian cancer indicates a host antitumor immune response and predicts improved survival. It is not well established whether the presence, distribution, or activity of TILs is different in metastatic tumor deposits as compared to the primary lesion. Between-site heterogeneity could explain the resistance of some tumors to immunotherapy and provide guidance for treating residual disease.
Design: We constructed a tissue microarray containing 1–2 primary tumors and 1–3 metastases from each of 50 patients (stages IIIC and IV) undergoing primary debulking of serous ovarian cancer between 2005 and 2008. Immunostains were performed for the immune markers CD3 (pan T lymphocyte), CD8 (cytotoxic T lymphocyte), and FoxP3 (regulatory T lymphocyte). For each stain, intraepithelial TIL density in triplicate cores was visually semi-quantitated on a scale from 0 to 3. Overall survival (OS) and disease-free survival (DFS) were derived from clinical and public records. Kaplan-Meier curves were compared by the log-rank test. To correct for multiple comparisons on the same data, p<0.0125 was considered significant.
Results: High intratumoral CD3+ TIL density averaged across all tumor sites (N=22 out of 50 patients) was significantly associated with favorable OS (p=0.0037), while high CD8+ and high FoxP3+ TIL density (N=29/50 and 22/50 patients, respectively) showed trends toward longer OS (p=0.0458 and p=0.0182, respectively). This effect was slightly less pronounced if only the TIL density of primary sites was considered. In cases having low FoxP3+ TIL density, a low FoxP3:CD8 ratio (seen in N=8/28 patients) predicted longer OS (p=0.0501). The OS of patients with homogeneously high (N=18) and with heterogeneous CD3+ TIL density (N=11) was significantly longer than that of patients with homogeneously low CD3+ density (N=21) (p=0.0069; Figure 1). DFS was not significantly associated with any measure of TIL density in this study.
Conclusions: Lymphocytic infiltration is correlated with overall survival in serous ovarian cancer. This effect is more pronounced when multiple tumor sites are evaluated. While the significance of between-site heterogeneity remains unclear, homogeneously low CD3+ TIL density is an adverse prognostic factor.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 139, Monday Morning