Journal Article

The Prognostic Significance of Cancer-Associated Fibroblasts in Esophageal Squamous Cell Carcinoma

Yeo, So-Young, Xuan, Yan-hiua, Ha, Sang Yun, Kim, Seok-Hyung

2014

Overview

Cancer-associated fibroblasts (CAF) are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC). We investigated CAF phenotype of ESCC based on histology and immunohistochemical expressions of five CAF markers such as fibroblast activation protein (FAP), smooth muscle actin (SMA), fibroblast-specific protein-1 (FSP1), platelet-derived growth factor receptor (PDGFRα), and PDGFRβ in 116 ESCC tissue samples. Besides, we also examined the correlation of the CAF phenotype with clinical relevance as well as other cancer-microenvironment related factors. Histologically immature CAF phenotype was correlated with poor prognosis (p<0.001) and associated with increased microvessel density, increased tumor associated macrophages, and epithelial to mesenchymal transition. CAF markers were characteristically expressed in stromal fibroblast close to tumor cells and the expression pattern of 5 CAF markers was highly heterogeneous in every individual cases. Of five CAF markers, SMA, FSP1, and PDGFRα were unfavorable prognostic indicators of ESCC. The number of positive CAF markers was greater in ESCC with immature CAFs than in those with mature ones. Our results demonstrate that histologic classification of CAF phenotype is a reliable and significant prognostic predictor in ESCC. CAF markers have the potential to be diagnostic and therapeutic targets in ESCC.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Actin / Actins - genetics / Actins - metabolism / Aged / Angiogenesis / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Breast cancer / Calcium-Binding Proteins - genetics / Calcium-Binding Proteins - metabolism / Cancer / Carcinoma, Squamous Cell - genetics / Carcinoma, Squamous Cell - metabolism / Carcinoma, Squamous Cell - mortality / Carcinoma, Squamous Cell - pathology / Chemotherapy / Classification / Colorectal cancer / Correlation / Diagnostic systems / Epithelial-Mesenchymal Transition - genetics / Esophageal cancer / Esophageal Neoplasms - genetics / Esophageal Neoplasms - metabolism / Esophageal Neoplasms - mortality / Esophageal Neoplasms - pathology / Esophageal Squamous Cell Carcinoma / Esophagus / Female / Fibroblast activation protein / Fibroblasts / Fibroblasts - metabolism / Fibroblasts - pathology / Gelatinases - genetics / Gelatinases - metabolism / Gene Expression / Genotype & phenotype / Growth factors / Health sciences / Histology / Humans / Macrophages / Macrophages - metabolism / Macrophages - pathology / Male / Markers / Medical prognosis / Medicine and Health Sciences / Membrane Proteins - genetics / Membrane Proteins - metabolism / Mesenchyme / Metastasis / Middle Aged / Morphology / Muscles / Pathology / Patients / Phenotype / Platelet-derived growth factor / Prognosis / Prostate / Proteins / Radiation therapy / Receptor, Platelet-Derived Growth Factor alpha - genetics / Receptor, Platelet-Derived Growth Factor alpha - metabolism / Receptor, Platelet-Derived Growth Factor beta - genetics / Receptor, Platelet-Derived Growth Factor beta - metabolism / Serine Endopeptidases - genetics / Serine Endopeptidases - metabolism / Smooth muscle / Squamous cell carcinoma / Stroma / Survival Analysis / Tissue Array Analysis / Tumor cells / Tumor Microenvironment - genetics / Tumors