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. 2018 Jun 18;16(1):110.
doi: 10.1186/s12957-018-1413-7.

MGMT promoter methylation and 1p/19q co-deletion of surgically resected pulmonary carcinoid and large-cell neuroendocrine carcinoma

Lei Lei  1 , Zhiming Jiang  1 , Gu Zhang  2 , Qiaoyuan Cheng  3 , Hongyang Lu  4   5
Affiliations

MGMT promoter methylation and 1p/19q co-deletion of surgically resected pulmonary carcinoid and large-cell neuroendocrine carcinoma

Lei Lei et al. World J Surg Oncol. .

Abstract

Background: 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. 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.

Methods: Nine 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).

Results: MGMT 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 (χ 2 = 7.565, P = 0.006).

Conclusions: MGMT 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.

Keywords: 1p/19q co-deletion; Large-cell neuroendocrine carcinoma; MGMT methylation; Pulmonary carcinoid.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Medical Ethics Committee of Zhejiang Cancer Hospital. The specimens of this study were obtained from the Biological Sample Bank of Zhejiang Cancer Hospital, and the patients signed the written informed consents to preserve their specimens in the Biological Sample Bank of Zhejiang Cancer Hospital for use in the research. In this retrospective study, one patient died, and exempt written informed consent was approved by the Medical Ethics Committee of the Zhejiang Cancer Hospital.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The results of MGMT promoter methylation and 1p/19q deletion for cases 3 and 5. Positive result for MGMT promoter methylation by pyrosequencing. The quantification results of ploidy (O:G): 1p was 14% and 19q was 22% in case 3; 1p was 50% and 19q was 4% in case 5. The arrows indicate a ratio of O:G < 0.87 in the cells. Magnification for HE is × 200. G green, O orange, he hematoxylin–eosin
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