Genetic changes in the spectrum of neuroendocrine lung tumors

BAGKGROUND, Recent classifications identify four categories of neuroendocri ne (NE) tumors of the lung: low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC), and high grade large cell neuroendocrine car cinoma (LC-NEC) and small cell lung carcinoma (SCLC). METHODS. The authors studied the molecular changes present in 59 archival N E tumors (10 TCs, 11 ACs, 18 LNECs, and 20 SCLCs). Utilizing microdissectio n 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 gen es. RESULTS. With the exception of ms gene mutations, the majority of these cha nges frequently were present in carcinomas and were present at lower freque ncies in carcinoids. LOH at one or more 3p regions was the most frequent ch ange found in the carcinoids. A relatively high incidence of LOH at the MEN 1 gene was common in all NE lung tumors. The incidence of LOH and p53 gene abnormalities progressively increased with increasing severity of turner ty pe. The patterns of p53 gene mutations were different between AC and high g rade NE tumors. LOH at 5q21 was correlated with poor survival in the carcin oid group. CONCLUSIONS. Although NE lung tumors have varied etiologies, the results of the current study support the clinicopathologic concept that they represen t a spectrum ranging from low grade TC to the highly malignant NE carcinoma s. Cancer 1999;85:600-7. (C) 1999 American Cancer Society.