Clinical implications of marker expression of Carcinoma-Associated Fibroblasts (CAFs) in patients with epithelial ovarian carcinoma after treatment with neoadjuvant chemotherapy

Cancer-associated fibroblasts (CAFs) play an important role in tumor initiation and progression. The aim of this study is to explore the role of 2 CAF markers, fibroblast activated protein (FAP) and α-smooth muscle actin (αSMA), in patients with epithelial ovarian cancer (EOC) post-neoadjuvant chemotherapy. Sixty-six patients with the diagnosis of EOC treated with debulking surgery after neoadjuvant therapy were retrieved from the archives. Immunohistochemistry for FAP and αSMA antibodies were performed on paraffin-embedded tissue. Fisher's exact test was performed to test the association between FAP and αSMA expression and disease status. Kaplan-Meier method with log-rank test was used to check the survival difference between different FAP tumor/stroma expressions. FAP stroma ^pos . expression was strongly associated with higher recurrences rate [OR: 15.95; 95 % CI: 1.521-835.206; p∈=∈0.0072]. Cases with combined FAP stroma ^pos and FAP tumor ^neg had higher death rate [OR: 4.845; 95 % CI: 1.53-16.61; p∈=∈0.0046] and higher recurrence rate [OR: 5.12; 95 % CI: 0.91-54.42; p∈=∈0.0487] compared to all the others. Cases with combined FAP stroma ^neg and FAP tumor ^neg were more likely to have lower recurrence rates [OR: 0.086; 95 % CI: 0.001-0.997; p∈=∈0.0248]. αSMA was expressed by tumor-associated stroma in 95 % of cases and by tumor cells in 9 % of cases. No statistical power was found for αSMA and disease status. Our data indicate that FAP plays an important role in predicting tumor aggressiveness in patients with EOC post-neoadjuvant therapy, and its frequent expression in this malignancy implicates that FAP targeted therapy could be a very attractive strategy.