Intraepithelial T cells and Prognosis in Ovarian Carcinoma: Novel Associations with Stage, Tumor Type and BRCA1 Loss

Genetic Pathology Evaluation Center of the Prostate Research Center, Department of Pathology, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver, BC, Canada.
Modern Pathology (Impact Factor: 6.19). 03/2009; 22(3):393-402. DOI: 10.1038/modpathol.2008.191
Source: PubMed


Intraepithelial tumor-infiltrating T cells have been correlated with improved outcomes in ovarian carcinoma, however, it is not known whether there is an association with disease stage, histological subtype, or BRCA mutation/expression. Two case series of ovarian carcinomas were included in the study; a retrospective series of 500 patients, and 40 prospectively collected cases fully characterized for BRCA1 mutation status and expression. Intraepithelial immune cells were assessed as present or absent by immunohistochemical staining of tissue microarrays. In the retrospective case series, the presence of intraepithelial CD8(+) T-cells correlated with improved disease-specific survival (P=0.027), whereas intraepithelial CD3(+) T cells did not (P=0.49). For serous ovarian carcinomas, the presence of intraepithelial CD3(+) and CD8(+) T-cells correlated with improved disease-specific survival (P=0.0016 and P<or=0.0001, respectively). The presence of intraepithelial CD8(+) T cells was not associated with improved survival in endometrioid or clear cell carcinomas. On multivariate analysis, disease stage and CD8(+) T cells were found to be independently predictive of improved disease-specific survival, whereas grade, age at surgery, and type of adjuvant treatment were not. In the prospective patient cohort, intraepithelial CD8(+) T-cells correlated with the presence of mutation or loss of expression of BRCA1 through promoter methylation (P=0.019). Intraepithelial CD8(+) tumor-infiltrating T-cells correlate with improved clinical outcomes for all stages of ovarian cancer; this association is restricted to the serous ovarian cancer subtype, and is an independent prognostic factor on multivariate analysis. The presence of intraepithelial CD8(+) T cells also significantly correlates with loss of BRCA1.

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    • "Furthermore, multivariate analysis showed that the presence of intratumoral T cells was an independent prognostic factor. Since then, several studies have confirmed the positive association between the presence of tumor infiltrating T cells and patient survival (5–8). The influence of intratumoral T cells on patient outcome indicates the immune system may play an antitumor role in ovarian cancer; however spontaneous regression of tumors through immune destruction is rare. "
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    • "It has long been established that EOC can stimulate host immune response and that the presence of infiltrating T cells, particularly CD8 + cytotoxic T lymphocytes (CTL), is associated with a better outcome [22] [23] [24] [25] [26]. In accordance with these studies, our results indicate better clinical outcome for the low-volume ascites group, whose tumors are characterized by more abundant tumor infiltrating cells. "
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    • "Cluster of differentiation 3 (CD3)+ TILs have been found to independently predict tumor recurrence and prolonged survival.42 Conversely, lack of TILs has been associated with poor survival.34,36–40 "
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