Expression of toll-like receptors in ovarian cancer

Purpose: Ovarian cancer continues to be the most lethal gynecologic malignancy, with a complex tumor microenvironment (TME). We investigated the immunohistochemical (IHC) expression of toll like receptors (TLRs) 4,5,7 and 9 together with CD68 and CD 163 as markers for tumor-associated macrophages (TAM) in relation to clinicopathological data. Methods: Data from 102 patients with serous ovarian cancer treated between 2006 and 2011 was retrospectively reviewed. A TLR IHC score was developed and CD68, CD163 density scores were calculated as the mean number of positive cells from three 0.5 mm(2) areas. Results: Advanced-stage disease (FIGO IIIC-IV) was present in 65.7% of cases. A TLR4 score above median was associated with peritoneal carcinomatosis (odds ratio/OR) 3.02, p=0.019) or ascites (OR 2.5, p=0.041). In FIGO stage IIIC-IV patients with a platinum free interval (PFI) >12 months had, in comparison with patients with PFI <= 12 months, a higher CD68 density score (191.9 +/- 95.2 vs. 152.7 +/- 69.4, p=0.066) and a lower CD163 density score (106.7 +/- 73.3 vs. 154.5 +/- 73.9, p=0.011). In early-stage ovarian cancer patients, TLR9 positivity was associated with a higher overall survival than in patients with absent expression (110.2 vs. 22 months, p<0.001), while advanced-stage patients with TLR7 positivity had a lower overall survival than patients with negative TLR7 (38.3 vs. 66.2 months, p=0.01). Conclusions: Our data shows that TLRs and TAM are important prognostic markers and future studies are needed to better comprehend the immune response in ovarian cancer.