Different Expression and Clinical Role of S100A4 in Serous Ovarian Carcinoma at Different Anatomic Sites

Abstract

The present study analyzed the site-specific expression and clinical role of S100A4 in advanced-stage ovarian carcinoma (OC). S100A4 expression was analyzed in 161 effusions, 67 primary carcinomas and 127 solid metastases using immunohistochemistry. S100A4 levels were additionally measured in 20 effusion supernatants using the immunofluorometric assay IFMA. Cytoplasmic and nuclear S100A4 was detected in cancer cells at all anatomic sites, while myofibroblasts in solid tumors expressed only cytoplasmic S100A4. Nuclear expression was higher in solid tumors than in effusions (p < 0.001), while stromal cell expression was higher in metastases than primary tumors (p = 0.001). IFMA analysis detected S100A4 in all 20 supernatants. Nuclear S100A4 expression in primary carcinomas (p = 0.049), FIGO stage IV (p = 0.019) and poor response to chemotherapy at diagnosis (p < 0.001) were associated with worse overall survival. All three parameters were independent prognosticators in Cox analysis (S100A4: p = 0.048, FIGO stage: p = 0.015, response to chemotherapy: p < 0.001). S100A4 is frequently expressed in tumor and host cells in OC, with upregulated stromal expression in solid metastases. Tumor cell nuclear S100A4 expression is higher in solid tumors than in effusions, and is associated with more aggressive clinical disease in primary carcinoma, suggesting that the tumor-promoting role of this molecule is predominantly exerted at this anatomic site.