Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki-67, budding uninhibited by benzimidazoles 3 (Bub-3) and sex-determining region Y-related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki-67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki-67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki-67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.