Analysis of K-ras, N-ras, H-ras, and p53 in lung neuroendocrine neoplasms.
This study screened 11 samples of typical carcinoid (TC), 4 samples of atypical carcinoid (AC), 1 sample of large cell neuroendocrine carcinoma (LCNEC), and four metastases for point mutations in exons 5 to 8 of the p53 gene, and exons 1 and 2 of the K-ras. H-ras, and N-ras genes using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) and direct sequencing and by immunohistochemistry for p53. Exon 1 of K-ras was mutated in two samples of low-grade AC and a metastasis from one of these tumors (GAT12 and AGT12, respectively). No mutations in N-ras or H-ras were found. Mutations in exons 5 and 8 of the p53 gene were identified in a high-grade AC and a LCNEC. Positive immunostaining for p53 was present in three samples, with only one genotypic mutation shown (LCNEC). In conclusion, point mutations of the p53 gene were infrequent in these pulmonary neuroendocrine tumors, did not correlate in all samples with immunostaining, and were associated with the higher-grade tumors. Second, the presence of K-ras mutations seems to be associated with the higher-grade carcinomas. Third, N-ras and H-ras mutations were not found with these pulmonary neuroendocrine tumors.
Couce
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ME
Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
Bautista
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Costa
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Carter
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D000328:Adult; D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53