Role of cancer-associated fibroblasts in oral squamous cell carcinomas, surgical margins, and verrucous carcinomas: An immunohistochemical study

BACKGROUND AND AIM: Cancer-associated fibroblasts (CAFs) are among the key tumor microenvironment components that determine tumor invasion, progression, and resistance to cancer therapeutics. Histologically normal mucosa adjacent to oral squamous cell carcinoma (OSCC) has been shown to harbor CAFs which aid in the loco-regional recurrence of the lesion. Verrucous carcinoma (VC), a low-grade variant of squamous cell carcinoma, has a better clinical outcome. However, few VCs show an aggressive biological course and necessitate wide excision with strict follow-up. Scarce literature is available regarding the role of CAFs in VCs. Thus, our study aimed to evaluate the frequency of CAFs in OSCC, normal mucosa adjacent to OSCC, and VC. METHODS: Thirty cases of squamous cell carcinoma, normal mucosa adjacent to OSCC, and VC each were included in the study. The sections were stained with an antibody against alpha-smooth muscle actin protein and CAF frequency was evaluated. RESULTS: The CAF frequency was highest in squamous cell carcinoma, followed by VC, and least in normal mucosa adjacent to OSCC (P<0.001). CONCLUSION: CAF frequency progressively increases with an increase in the grade or biological behavior of the lesion. Thus, screening CAF frequency in these benign and malignant oral lesions is necessary for better treatment outcomes. RELEVANCE FOR PATIENTS: The immunohistochemical screening for CAFs in OSCC and VC can serve as an integrated approach for the development of a directed treatment plan that leads to a better patient prognosis. Routine assessment of CAF frequency in surgical margins can serve as an adjunct in determining clear margins and possible locoregional recurrence. Furthermore, target therapy for CAFs can be used to minimize possible recurrence and distant metastasis.