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Genetic changes in the spectrum of neuroendocrine lung tumors
Author(s) -
Onuki Naoyoshi,
Wistuba Ignacio I.,
Travis William D.,
Virmani Arvind K.,
Yashima Kazuo,
Brambilla Elizabeth,
Hasleton Phillip,
Gazdar Adi F.
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990201)85:3<600::aid-cncr10>3.0.co;2-w
Subject(s) - loss of heterozygosity , men1 , microdissection , neuroendocrine tumors , pathology , lung , carcinoid tumors , carcinoma , lung cancer , small cell lung carcinoma , medicine , cancer research , large cell , biology , small cell carcinoma , cancer , multiple endocrine neoplasia , gene , adenocarcinoma , allele , genetics
Abstract BACKGROUND Recent classifications identify four categories of neuroendocrine (NE) tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). METHODS The authors studied the molecular changes present in 59 archival NE tumors (10 TCs, 11 ACs, 18 LNECs, and 20 SCLCs). Utilizing microdissection and polymerase chain reaction‐based assays, the authors examined loss of heterozygosity (LOH) at ten chromosomal regions frequently deleted in lung tumors (3p, 5q, 11q, 13q, and 17 p) and for mutations at the p53 and ras genes. RESULTS With the exception of ras gene mutations, the majority of these changes frequently were present in carcinomas and were present at lower frequencies in carcinoids. LOH at one or more 3p regions was the most frequent change found in the carcinoids. A relatively high incidence of LOH at the MEN1 gene was common in all NE lung tumors. The incidence of LOH and p53 gene abnormalities progressively increased with increasing severity of tumor type. The patterns of p53 gene mutations were different between AC and high grade NE tumors. LOH at 5q21 was correlated with poor survival in the carcinoid group. CONCLUSIONS Although NE lung tumors have varied etiologies, the results of the current study support the clinicopathologic concept that they represent a spectrum ranging from low grade TC to the highly malignant NE carcinomas. Cancer 1999;85:600–7. © 1999 American Cancer Society.