K-RAS GENE POINT MUTATION - A STABLE TUMOR-MARKER IN NONSMALL CELL LUNG-CARCINOMA

K-ras gene point mutation is a highly frequent event in human malignan cy. About one third of non-small cell lung cancer (NSCLC) patients har bor K-ras gene point mutational activations. This study investigates t he prevalence of K-ras mutation in autopsy tumors with NSCLC, and the correlation of K-ras gene point mutations between primary tumors and m etastases in NSCLC. Formalin-fixed, paraffin-embedded tissue sections of 15 primary lung tumors and their metastases, (obtained from autopsy ), were examined for the presence of point mutations in K-ras gene cod on 12, 13 and 61 by oligodeoxynucleotide hybridization analysis of DNA fragments, amplified by polymerase chain reaction (PCR). K-ras gene p oint mutations were detected in rive cases of lung carcinoma, of which four were adenocarcinomas and one was squamous cell carcinoma. In eac h of these cases, identical K-ras gene mutations were found in the DNA of both the primary tumor and its corresponding distant metastases. A ctivating K-ras base-substitutions correlate well between the primary tumor and its corresponding metastases in NSCLC. In the negative cases where no K-ras mutation was found in the primary tumors, no newly acq uired K-ras mutation appeared in the metastases. Our study indicates t hat K-ras point mutation serves as a stable tumor marker in NSCLC.