Abstract

BackgroundThe response to temozolomide (TMZ) treatment in small-cell lung cancer (SCLC) correlated with O(6)-methylguanine -DNA methyltransferase (MGMT) promoter methylation. 1p/19q co-deletion within oligodendroglioma is a responsive predictor for TMZ. Currently, the status of MGMT promoter methylation and 1p/19q co-deletion in pulmonary carcinoid (PC) and large-cell neuroendocrine carcinoma (LCNEC) is not reported.MethodsNine PC [two atypical carcinoids (AC), seven typical carcinoids (TC)] and six LCNEC patients were collected retrospectively. The pyrosequencing and fluorescence in situ hybridization were used to detect the MGMT promoter methylation and 1p/19q co-deletion in surgically resected specimens. Kaplan–Meier analysis was used to assess the rate of disease-free survival (DFS).ResultsMGMT promoter methylation was found in two (2/6, 15.3%) LCNEC patients but not in any PC patients. Three (3/6, 50%) 1p and two (2/6, 33.3%) 19q single deletions were found in LCNEC patients. One 1p single deletion was found in AC patients. One (1/7, 14.3%) 1p and two (2/7, 28.6%) 19q single deletions were found in TC patients. After a median follow-up of 38 months, three LCNEC patients developed distant metastasis and one patient died of LCNEC disease. The DFS of PC patients was much longer than LCNEC patients (χ2 = 7.565, P = 0.006).ConclusionsMGMT promoter methylation and 1p/19q co-deletion might not be the ideal biomarkers for TMZ treatment in TC/AC patients. Thus, the detection of MGMT promoter methylation and whether it can be used as a medication for TMZ in LCNEC patients necessitates investigation. Furthermore, 1p deletion could be a negative prognostic factor for LCNEC patients.

Highlights

  • The response to temozolomide (TMZ) treatment in small-cell lung cancer (SCLC) correlated with O(6)methylguanine -DNA methyltransferase (MGMT) promoter methylation. 1p/19q co-deletion within oligodendroglioma is a responsive predictor for TMZ

  • Three (50%) 1p single deletion and two (33.3%) 19q single deletions were found in large-cell neuroendocrine carcinoma (LCNEC) patients (Fig. 1 and Additional file 1: Figure S1). 1p single deletion was found in one atypical carcinoids (AC) patient

  • We found that 44.4% of pulmonary carcinoid (PC) were females, typical carcinoids (TC) were more than ACs (77.8 vs. 22.2%), and only one male patient was a smoker (11.1%) in nine PCs with a median age of 50 (41–63) years

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Summary

Introduction

The response to temozolomide (TMZ) treatment in small-cell lung cancer (SCLC) correlated with O(6)methylguanine -DNA methyltransferase (MGMT) promoter methylation. 1p/19q co-deletion within oligodendroglioma is a responsive predictor for TMZ. The response to temozolomide (TMZ) treatment in small-cell lung cancer (SCLC) correlated with O(6)methylguanine -DNA methyltransferase (MGMT) promoter methylation. The status of MGMT promoter methylation and 1p/ 19q co-deletion in pulmonary carcinoid (PC) and large-cell neuroendocrine carcinoma (LCNEC) is not reported. Patients with pulmonary carcinoid (PC) tumors and low grade (typical carcinoid (TC)) and intermediate grade (atypical carcinoid (AC)) neuroendocrine tumors accounted for 1% of the lung cancer patients undergoing surgical treatment [1, 2]. The response to TMZ treatment in small-cell lung cancer (SCLC) may be associated with O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation [8]. 1p/19q co-deletion is a positive response biomarker for TMZ treatment in oligodendrogliomas [9] and SCLC [10]. In order to elucidate the status of MGMT methylation and 1p/19q co-deletion in PC and LCNEC patients, two cases of AC, seven cases of TC, and six cases of LCNEC patients who underwent surgery were assimilated retrospectively and studied from the Zhejiang Cancer Hospital in China between 2008 and 2016

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