Intraepithelial T cells and tumor proliferation

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Abstract
BACKGROUND: The aim of the study was to determine whether tumor‐infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction. METHODS: Snap‐frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3+, CD8+, FoxP3+ tumor‐infiltrating lymphocytes, and Ki67 expression. Kaplan‐Meier survival curves were estimated and compared using a log‐rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios. Interactions were modeled using recursive partitioning based on maximal prognostic differentiation. RESULTS: Brisk intraepithelial CD8+ cells (P = .035) and low Ki67 expression (P = .042) portended prolonged survival. The T‐cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8+ frequency had a 5‐year survival rate of 73.3%. Patients with aggressive tumor behavior, that is, whose tumors exhibited low frequency of intraepithelial CD8+ T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8+ T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking. CONCLUSIONS: For the first time, these novel interactions of T cells, tumor proliferation index, and surgical treatment reveal that biological prognosticators may be useful for surgical decision making in ovarian cancer. Cancer 2009. © 2009 American Cancer Society.