• betel quid;
  • buccal mucosa;
  • oral squamous cell carcinoma;
  • RAR-β


Background:  Within the abundant retinoids nuclear receptors, abnormally low expression of the RAR-β has been shown to contribute to neoplastic progression in oral epithelium in western countries. Distinctly different risk factors contributing to oral squamous cell carcinoma (OSCC) in epidemiologically different societies denote the value of exploring the role of RAR-β expression in OSCC associated with betel quid (BQ) use in our society.

Methods:  We examined the cellular expression of RAR-β using in situ hybridization (ISH) analysis on 38 pairs of surgical specimens of primary OSCC and non-cancerous matched tissues (NCMT) to correlate with their clinico-pathological features including age, sites of tumor, habit of BQ use, stage, size of primary tumor, lymph node metastasis, differentiation.

Results:  Of all cases analyzed, BQ users were significantly younger than non-BQ users (51.2 ± 2.1 vs. 60.2 ± 2.6, P= 0.01). 52% OSCC of BQ users (13/25) and 23% OSCC of non-BQ users (3/13) exhibited the absence of RAR-β expression. In 17 paired-samples from buccal mucosa (BM), most NCMT and less than half of OSCC exhibited RAR-β expression (16/17, 94% vs. 8/17, 47%, P= 0.003). The RAR-β expression was seen in the vast majority of the well-differentiated OSCC and in less than half of the moderately differentiated OSCC only (15/20, 75% vs. 7/18, 39%, P= 0.03).

Conclusion:  A correlation between the loss of RAR-β expression and more advanced histopathological grade tumors was observed. This study also suggests that the loss of RAR-β expression is significant in BM OSCC, which preferentially occurs in BQ users.