Infrequent Mutations of the p53 Gene in Pulmonary Carcinoid Tumors

Archival specimens of 25 pulmonary carcinoids including 15 cases of typical carcinoid, 9 atypical carcinoids, and 1 large-cell neuroendocrine carcinoma were analyzed for mutations in exons 5 to 8 of the p53 gene. 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 carcinoids, a tumor type without epidemiological link to cigarette smoking, were G to A transitions. The level of p53 protein was investigated by immunohistochemis-try 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 antibodies pAbl801 and DO-1. Our data suggest that point mutations of the pS3 gene are infrequent in pulmonary carcinoids thus contrasting the findings in other histological types of lung cancer, in particular small-cell lung cancer. Moreover, negative immunostaining for p53 is no indicator for the absence of pS3 missense mutations in typicalcarcinoids.