Expression of O(6)-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm

Int J Clin Exp Pathol. 2014 Jun 15;7(7):4204-12. eCollection 2014.

Abstract

O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O(6)-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (χ(2) = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP-NEN.

Keywords: Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN); O5-methylguanine-DNA methyltransferase (MGMT); immunohistochemisty; survival.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • DNA Modification Methylases / analysis
  • DNA Modification Methylases / biosynthesis*
  • DNA Repair Enzymes / analysis
  • DNA Repair Enzymes / biosynthesis*
  • Digestive System Neoplasms / enzymology*
  • Digestive System Neoplasms / mortality
  • Digestive System Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / enzymology*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology*
  • Prognosis
  • Proportional Hazards Models
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / biosynthesis*
  • Young Adult

Substances

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