DETECTION OF K-RAS MUTATIONS IN RESECTED PRIMARY LEIOMYOSARCOMA

Mutation of the K-ras oncogene occurs frequently in human malignancy, However, there are few reports concerning K-ras mutations in soft-tiss ue sarcoma, including leiomyosarcoma, We therefore designed a study to determine the prevalence of mutations in the first exon of K-ras in l eiomyosarcoma and to evaluate its prognostic potential, Fifty-one leio myosarcomas were reviewed, and their diagnoses were confirmed on patho logical review, Tissue blocks were retrieved, and new sections were pr epared for confirmation of diagnosis, Additional tissue sections were used for DNA isolation, PCR and denaturing gradient gel electrophoresi s (DGGE) were used to detect K-ras mutations in the first exon of geno mic DNA isolated from the specimens, Seven (14%) K-ras mutations were detected using DGGE. Subsequent sequencing of the K-ras gene from each of the mutated tumors confirmed the DGGE results in each case. The me dian survival for patients whose tumors did not contain mutations of K -ras was 42 months (n = 42) versus 25 months (n = 7) for those with mu tations (P = 0.06), However, patients with stages I and II tumors had a median survival of 82 months (n = 28) compared to 28 months for thos e with stages III and IV disease (n = 20, P = 0.02), The results sugge st that K-ras codon 12 mutations are uncommon in leiomyosarcoma; howev er, when such mutations are found, there is a trend toward worse survi val, Furthermore, the data confirm that stage is a significant prognos tic indicator.