Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

Cancer microenvironment : official journal of the International Cancer Microenvironment Society(2013)

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摘要
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.
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关键词
Cancer-associated fibroblasts (CAF), Epithelial ovarian cancer (EOC), Neoadjuvant therapy, Disease outcome
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