TY - JOUR
T1 - Genetic changes in the spectrum of neuroendocrine lung tumors
AU - Onuki, Naoyoshi
AU - Wistuba, Ignacio I.
AU - Travis, William D.
AU - Virmani, Arvind K.
AU - Yashima, Kazuo
AU - Brambilla, Elizabeth
AU - Hasleton, Phillip
AU - Gazdar, Adi F.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - 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 17p) 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.
AB - 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 17p) 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.
KW - Chromosome 3p
KW - Chromosome 5q
KW - MEN1 gene
KW - Neuroendocrine tumors
KW - Pulmonary carcinoids
KW - Small cell carcinoma of the lung
KW - p53 gene
KW - ras gene
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U2 - 10.1002/(SICI)1097-0142(19990201)85:3<600::AID-CNCR10>3.0.CO;2-W
DO - 10.1002/(SICI)1097-0142(19990201)85:3<600::AID-CNCR10>3.0.CO;2-W
M3 - Article
C2 - 10091733
AN - SCOPUS:0033083898
SN - 0008-543X
VL - 85
SP - 600
EP - 607
JO - Cancer
JF - Cancer
IS - 3
ER -