Premalignant cervical lesions are characterized by dihydrofolate reductase gene amplification and c-Myc overexpression: possible biomarkers.

OBJECTIVE: The c-Myc oncoprotein deregulation is associated with overall genomic instability and locus-specific genomic instability involving the dihydrofolate reductase (DHFR) locus. This study analyzes c-Myc protein levels and the stability of the DHFR gene in cervical tissue biopsies. MATERIALS AND METHODS: The stability of the DHFR gene was examined by fluorescence in situ hybridization (FISH). c-Myc protein levels were evaluated using quantitative fluorescent immunohistochemistry. Forty-four cervical tissue biopsies were analyzed and included 33 preinvasive cervical lesions identified by histology, 14 samples were cervical intraepithelial neoplasia (CIN) 1; 7 were CIN 2; and 12 were CIN 3. Eleven biopsies had negative histology. RESULTS AND CONCLUSION: c-Myc protein levels were elevated in CIN 1, 2, and 3 (p = .02) biopsies. Concomitantly, DHFR gene amplification was detected in CIN 1, 2, and 3 (p = .0001). The degrees of DHFR gene amplification and of c-Myc protein levels were a measure of the progressive degree of the lesion.