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.


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.


CONCLUSIONS
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.
Guijon
Fernando B
FB
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. guijon@cc.umanitoba.ca
Greulich-Bode
Km
K
Paraskevas
Maria
M
Baker
Patricia
P
Mai
Sabine
S
D014408:Biomarkers, Tumor; D003127:Colposcopy; D020732:Cytogenetic Analysis; D005260:Female; D005629:Frozen Sections; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D013762:Tetrahydrofolate Dehydrogenase