DNA Adducts, Chromosomal Instability, EMT, and GSTM1 in Oral Squamous Cell Carcinoma.

PURPOSE: To determine whether DNA-adduct burden, chromosomal instability, epithelial-mesenchymal transition, and glutathione S-transferase M1 (GSTM1) genotype are independently associated with advanced-stage oral squamous cell carcinoma or overall survival.

METHODS

We studied 160 patients with histologically confirmed oral squamous cell carcinoma. DNA-adduct burden was measured by 32P-postlabeling, validated against mass spectrometry in 50 patients; chromosomal instability by fluorescence in situ hybridization of chromosomes 7, 9, and 11; epithelial-mesenchymal transition by E-cadherin/vimentin immunohistochemistry; and GSTM1 genotype by multiplex polymerase chain reaction. Logistic and Cox regression were performed.

RESULTS

DNA-adduct burden and epithelial-mesenchymal transition score were strongly correlated (r = 0.923, p < 0.001), but neither differed by tumor stage. None of the four markers was independently associated with advanced-stage disease. During follow-up, 48 patients died. Nodal positivity (hazard ratio 3.84, 95% confidence interval 2.00-7.38, p < 0.001) and Stage IV disease (hazard ratio 7.82, 95% confidence interval 2.12-28.84, p = 0.002) were independently associated with poorer survival. The combined clinical-molecular model showed modest discrimination (AUC 0.689).

CONCLUSION

Nodal status and advanced stage were the dominant independent determinants of survival, with routine nodal assessment improving prognostic discrimination beyond stage alone. The four molecular markers tracked with disease characteristics but added no independent prognostic value, warranting replication in larger, prospective cohorts.