I Murakami, Y Fujiwara, N Yamaoka, K Hiyama, S Ishioka and M Yamakido
Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.

In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting before starting treatment, we screened for p53 gene mutations in tumor specimens obtained using diagnostic methods such as fiberoptic bronchoscopy, thoracentesis, and percutaneous needle aspiration. We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique. 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 cytopathologic examination in detecting malignant cells. The type and location of the p53 gene mutation was the same in cytologically positive specimens 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 mutation for each histologic subtype was comparable to previously published data examining surgically and/or autopsy-obtained specimens. These results indicate that detection of p53 gene mutations in a nonsurgical, diagnostic setting is feasible. This technique will make it possible to assess the significance of p53 gene mutations in relation to survival and response to therapy before starting treatment, in future prospective studies.

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