INFREQUENT MUTATIONS OF THE P53 GENE IN PULMONARY CARCINOID-TUMORS

Archival specimens of 25 pulmonary carcinoids including 15 cases of ty pical carcinoid, 9 atypical carcinoids, and 1 large-cell neuroendocrin e carcinoma were analyzed for mutations in exons 5 to 8 of the p53 gen e. Mutations were identified in 4 tumors, including 3 out of 15 (20%) typical carcinoids and the single large-cell neuroendocrine carcinoma, but none of the atypical carcinomas showed a mutation. The mutations were acquired during tumor development since they were not present in the corresponding nontumorous tissue. All mutations in the typical car cinoids, a tumor type without epidemiological link to cigarette smokin g, were G to A transitions. The level of p53 protein was investigated by immunohistochemistry with the polyclonal antibody CM-1. None of the pulmonary carcinoids investigated showed a positive reaction, despite the presence of missense mutations in two cases. Negative staining of carcinoids with mutations was also observed with the monoclonal antib odies pAb1801 and DO-1. Our data suggest that point mutations of the p 5.3 gene are infrequent in pulmonary carcinoids thus contrasting the f indings in other histological types of lung cancer, in particular smal l-cell lung cancer. Moreover, negative immunostaining for p53 is no in dicator for the absence of p53 missense mutations in typical carcinoid s.