RELATIONSHIPS BETWEEN C-KI-RAS MUTATIONS, HPV TYPES, AND PROGNOSTIC INDICATORS IN INVASIVE ENDOCERVICAL ADENOCARCINOMAS

Objective. Ras gene mutations have been identified in squamous cell carcinomas of the cervix and are associated with advanced-stage tumors. The current study was designed to determine the prevalence of c-Ki-ras mutations in invasive endocervical adenocarcinomas and associations between mutations, HPV status, and known prognostic indicators. Methods. Paraffin-embedded tissue samples from 32 cases of invasive adenocarcinoma of the endocervix were analyzed for the presence of c-Ki-ras mutations by amplification of DNA extracted from paraffin blocks using the polymerase chain reaction (PCR) and subsequent restriction enzyme digestion of the amplimers. This method allows detection of aspartic acid mutations of the c-Ki-ras gene at codons 12 and 13. Samples were also analyzed for the presence of HPV DNA using PCR and either ‘consensus sequence’ primers or ‘type-specific’ primers for HPVs 16 and 18. Patients’ charts were reviewed for clinical information and correlations between clinical outcome and known prognostic indicators and the presence of c-Ki-ras mutations was assessed. Results. c-Ki-ras codon 12 mutations were detected in only 4 of the 32 cases (12.5%) of invasive endocervical adenocarcinomas examined. No codon 13 mutations were detected. Fifty-nine percent of the cases were HPV 16 or HPV 18 DNA positive and only 1 of the 4 cases with a codon 12 mutation was associated with HPV 16 or HPV 18. There were no significant associations between stage or grade of tumor or outcome and the presence of codon 12 mutations. However, using the observed survival as computed by the Berkson Gage Method at 12 months, the estimated median survival for patients with c-Ki-ras codon 12 mutations is 29 months compared to 68 months for patients lacking codon 12 mutations. Conclusions. These results indicate that c-Ki-ras codons 12 and 13 mutations are uncommon in invasive endocervical adenocarcinomas. © 1993 Academic Press, Inc.