Prognostic value of the immunohistochemical detection of cancer‐associated fibroblasts in oral cancer: A systematic review and meta‐analysis

• Published in: Journal of oral pathology & medicine Vol. 47; no. 5; pp. 443 - 453
• Main Authors: Dourado, Mauricio Rocha, Guerra, Eliete N. S., Salo, Tuula, Lambert, Daniel W., Coletta, Ricardo D.
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.05.2018
• Subjects: Actin; Actins - metabolism; alpha smooth muscle actin; Biomarkers, Tumor - metabolism; Cancer; cancer‐associated fibroblast; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Databases, Bibliographic; Dentistry; Disease-Free Survival; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Humans; Immunohistochemistry; Medical prognosis; Meta-analysis; Metastases; Mouth Neoplasms - diagnosis; Mouth Neoplasms - mortality; Mouth Neoplasms - pathology; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Prognosis; Smooth muscle; Squamous cell carcinoma; Statistical analysis; Stroma; Survival; cancer-associated fibroblast; alpha smooth muscle actin; prognosis; oral cancer
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.12623

Aim To perform a meta‐analysis to assess whether the presence of cancer‐associated fibroblasts (CAF) is a prognostic marker of oral squamous cell carcinomas (OSCC). Methods Immunohistochemical studies assessing the prognostic relevance of CAF (alpha smooth muscle actin (α‐SMA)‐positive fibroblasts) in patients with OSCC were systematically reviewed using Cochrane, Lilacs, PubMed, Scopus, and Web of Science databases. The outcomes assessed were overall survival (OS) and disease‐free survival (DFS). The meta‐analysis was performed using the random‐ and fixed‐effects model with adjusted hazard ratio (HR) and 95% confidence intervals (95% CI) as effect measures. The methodological quality of the included studies was assessed using the Meta‐Analysis of Statistics Assessment and Review Instrument (MAStARI) tool, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system. Results The presence of high levels of CAF in the stroma of OSCC predicted shortened time to DFS (HR = 3.32, 95% CI: 2.09‐5.26, P < .00001) and an overall decrease in survival (HR: 2.16, 95% CI: 1.60‐2.92, P < .00001). Moreover, high presence of CAF was frequently reported in association with parameters that worsen the prognosis in OSCC, including advanced disease stage (TNM classification), recurrence, tumor grade, depth of invasion, vascular, lymphatic and neural invasion, and extranodal metastatic spread. Conclusion The presence of CAF, as assessed by α‐SMA‐positive fibroblasts in the stroma, indicates poor prognosis in patients with OSCC.