Intratumoral immune cells and ERCC1 expression are likely to play a role in the response of ovarian
carcinoma to
chemotherapy, but their impact on
therapy outcome is still unclear. Therefore, 41 cases of optimally resected high grade serous ovarian
carcinomas were examined retrospectively for stromal and intraepithelial lymphocyte populations and ERCC1 status in relation to response to
platinum-based
therapy. Based on RECIST criteria, 27 patients were classified as responsive and 14 as
therapy resistant, respectively. Using immunohistochemistry for CD3, CD8, CD4, TIA1, MUM1 and FOX P3 on representative
tumor sections, we quantitatively evaluated the intratumoral density of lymphocyte subpopulations. In addition, ERCC1
protein and
mRNA expression were determined by immunohistochemistry using the Steffensen score and quantitative RT-PCR, respectively. Furthermore, ERCC1 SNP's C8092A and
codon 118 were analysed. Response to
chemotherapy was significantly associated with higher numbers of stromal CD3+ (mean 21.33 lymphocytes/HPF versus 8.21 lymphocytes/HPF, p = 0.002) and CD8+ lymphocytes (mean 9.22 lymphocytes/HPF versus 4.57 lymphocytes/HPF, p = 0.013). Counts of intraepithelial CD3+ and CD8+ lymphocytes, stromal and intraepithelial FOXP3+ and TIA1+ cells, CD4+ lymphocytes, and MUM1+ plasma cells did not reach statistical significance. Neither ERCC1
protein expression (p = 0.232) nor SNPs
codon 118 and C8092A of the ERCC1 gene (p = 0.269 and p = 0.543) showed an association with
therapy response. The same was true for ERCC1
mRNA levels (p = 0.896), probably due to intratumoral lymphocyte contamination. In conclusion, the density of CD3+ and CD8+ T-cells in
tumor stroma proved to be a significant predictor for response to
platinum-based
therapy, whereas examination of ERCC1 failed to identify
therapy-responsive patients.