1. ¹Genetic Pathology Evaluation Center of the Prostate Research Center, Department of Pathology, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver, BC, Canada
2. ²Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada
3. ³Department of Pathology, Stanford University Medical Center, Stanford, CA, USA
4. ⁴Center for Research on Ovarian Cancer Early Detection and Cure, University of Pennsylvania, Philadelphia, PA, USA

Correspondence: Professor CB Gilks, MD, Genetic Pathology Evaluation Center of the Prostate Research Center, Department of Pathology, Vancouver General Hospital and British Columbia Cancer Agency, Room 1259, 1st Floor JPPN, 855 West 12th Avenue, Vancouver, BC, V5Z 1M9 Canada. E-mail: Blake.Gilks@vch.ca

⁵These authors contributed equally to this work.

Received 30 June 2008; Revised 13 October 2008; Accepted 19 October 2008; Published online 5 December 2008.

Abstract

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 P0.0001, 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.