DETECTION OF P53 GENE-MUTATIONS IN CYTOPATHOLOGY AND BIOPSY SPECIMENSFROM PATIENTS WITH LUNG-CANCER

In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting befor e starting treatment, we screened for p53 gene mutations in tumor spec imens obtained using diagnostic methods such as fiberoptic bronchoscop y, thoracentesis, and percutaneous needle aspiration. We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiros hima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis tech nique. p53 gene mutations were found in 64 of 159 (40%) cytologically positive specimens, but in none of 47 cytologically negative specimens . The PCR-based assay did not increase the sensitivity of the cytopath ologic examination in detecting malignant cells. The type and location of the p53 gene mutation was the same in cytologically positive speci mens obtained by different methods, but from the same patient. Of the 66 patients, p53 gene mutations were found in 27 (41%) at the time of the first nonsurgical diagnostic examination: 7 of 12 (58%) with small cell carcinoma, 9 of 20 (45%) with squamous cell carcinoma, and 11 of 34 (32%) with adenocarcinoma of the lung. The incidence of p53 gene m utation for each histologic subtype was comparable to previously publi shed data examining surgically and/or autopsy-obtained specimens. Thes e results indicate that detection of p53 gene mutations in a nonsurgic al, diagnostic setting is feasible. This technique will make it possib le to assess the significance of p53 gene mutations in relation to sur vival and response to therapy before starting treatment, in future pro spective studies.