Uterine cervical dysplasia and cancer: identification of c-myc status by quantitative polymerase chain reaction.
The c-myc oncogene status was determined in patients with nondysplasia (ND; 9 patients), low-grade squamous intraepithelial lesion (LGSIL; 12 patients), high-grade squamous intraepithelial lesion (HGSIL; 21 patients) and invasive squamous cell carcinoma (ISCC; 20 patients) of uterine cervix using fluorescent quantitative polymerase chain reaction (PCR). In the same paraffin-embedded specimens, other potential risk factors were also screened: human papillomavirus (HPV) infection, Ha-ras codon 12 mutation, DNA aneuploidy. Gene amplification, identified as c-myc copy numbers greater than the mean value +2 SD of patients with ND, was seen in 44% patients with LGSIL, 76% patients with HGSIL, and 67% patients with ISCC. These data indicate that c-myc amplification is one of the critical early events in the progression of uterine cervical lesions. HPV infection of various subtypes was identified in 0% patients with ND, 55% patients with LGSIL, 95% patients with HGSIL, and 84% patients with ISCC. No codon 12 mutation of the Ha-ras gene was found in this series. Aneuploid DNA pattern was seen in 0% patients with ND, 58% patients with LGSIL, 90% patients with HGSIL, and 80% patients with ISCC. There was a significant correlation between HPV infection and DNA aneuploidy. However, no relationship was seen between c-myc status and other factors in this series. Patients with HGSIL and ISCC almost always (95%) had multiple risk factors, whereas more than half of the patients with LGSIL had no or only one risk factor (P = 0.0001).
Aoyama
C
C
Department of Pathology, Olive View-UCLA Medical Center, Sylmar, CA 91342, USA.
Peters
J
J
Senadheera
S
S
Liu
P
P
Shimada
H
H
D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc