Analysis of cancer-associated fibroblasts and the epithelial-mesenchymal transition in cutaneous basal cell carcinoma, squamous cell carcinoma, and malignant melanoma

Activated cancer-associated fibroblasts (CAFs) and fibroblasts that have undergone the epithelial-mesenchymal transition (EMT) in cancer stroma contribute to tumor progression and metastasis. However, no reports have investigated the CAF phenotype and its clinicopathological relevance in cutaneous malignant tumors, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Here, we investigated the CAF phenotype in cutaneous malignant tumors based on their histology and immunohistochemical expression of CAF-related markers, including adipocyte enhancer-binding protein 1 (AEBP1), podoplanin, platelet-derived growth factor receptor alpha (PDGFR alpha), PDGFR beta, fibroblast activating protein (FAP), CD10, S100A4, alpha-smooth muscle actin (alpha-SMA), and EMT-related markers (Zebl, Slug, and Twist). In addition, we assessed the role of the CAF phenotype in cutaneous malignant cancers using hierarchical cluster analysis. Consequently, 3 subgroups were stratified based on the expression pattern of CAF and EMT-related markers. Subgroup 1 was characterized by low expression of AEBP1, PDGFR alpha, PDGFR beta, FAP and Slug, whereas subgroup 2 was closely associated with high expression of PDGFR beta, S100A4 and Twist. In addition, high expression levels of podoplanin, PDGFR beta, CD10, S100A4, alpha-SMA, Zebl , Slug and Twist were observed in subgroup 3. High expression of CD10 was commonly found in all 3 subgroups. These subgroups were correlated with histologic subtypes, that is, subgroup 1, MM; subgroup 2, BCC; and subgroup 3, SCC. We suggest that the expression pattern of CAF- and EMT-related proteins plays crucial roles in the progression of BCC, SCC, and MM. (C) 2018 The Authors. Published by Elsevier Inc.