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

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

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.

MeSH terms

  • Adult
  • Aged
  • Carcinoid Tumor / genetics*
  • Carcinoid Tumor / surgery
  • Carcinoma, Large Cell / genetics*
  • Carcinoma, Large Cell / surgery
  • Carcinoma, Neuroendocrine / genetics*
  • Carcinoma, Neuroendocrine / surgery
  • China
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • DNA Methylation / genetics
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Tumor Suppressor Proteins / genetics*

Substances

  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes

Supplementary concepts

  • Chromosome 1, monosomy 1p