Telomerase reverse transcriptase promoter region mutations and the clinical characteristics of pulmonary neuroendocrine tumors

Background: Pulmonary neuroendocrine tumors (NETs) represent approximately 20-25% of all primary lung tumors. It is occasionally difficult to distinguish between the different types of pulmonary NETs. Telomerase reverse transcriptase (TERT) can effectively maintain the structural integrity of telomeres. Alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may be a useful tool for the differential diagnosis among different kinds of NETs. There is no report about TERT promoter mutations in pulmonary NETs in China. This study aimed to clarify the status of TERT promoter region mutations and the clinical characteristics of pulmonary NETs. Methods: A total of 41 surgically resected pulmonary NETs were retrospectively collected from the Zhejiang Cancer Hospital in China between 2008 and 2016, including typical carcinoid (TC) cases, atypical carcinoid (AC) cases, large cell neuroendocrine carcinoma (LCNEC) cases, and small cell lung carcinoma (SCLC) cases. TERT promoter mutation was analyzed by polymerase chain reaction (PCR) amplification and Sanger sequencing. The clinical characteristics and treatment data were also collected. The survival time of all patients was followed-up. Results: Most pulmonary NET patients were male. Most SCLC patients were heavy smokers, while most AC/TC patients were non-smokers. No TERT promoter region 124 (C228T) and 146 (C250T) mutations were found in the 41 cases of pulmonary NET. The prognosis of AC/TC was the best, followed by LCNEC, while SCLC was the worst. Overall survival (OS) of the SCLC patients <= 65 years (n=23) and >65 years (n=6) were 35 and 18 months, respectively, P=0.041. SCLC patients who received >= 3 cycles of adjuvant chemotherapy (n=18) had longer OS as compared to those who received <= 2 cycles of adjuvant chemotherapy (n=11) (not reach vs. 22 months, P=0.061). Conclusions: TERT promoter mutations are rare in pulmonary NET. The prognosis of different histological subtypes of pulmonary NET varies. Age and cycles of adjuvant chemotherapy are related to prognosis of resected SCLC.