Methylguanine Methyltransferase (MGMT) Expression in Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas
Amanda Treece, Leona Council, James Posey III, Shuko Harada. University of Alabama, Birmingham, AL
Background: Methylguanine methyltransferase (MGMT) is a tumor suppressor gene located on chromosome 10 that removes adducts from O6-guanine in DNA which could result in cell death or carcinogenesis. Loss of expression, often by hypermethylation of promoter regions, has been documented in several cancers. MGMT methylation has been associated with longer survival in patients with glioblastoma multiforme undergoing treatment with temozolomide. Loss of MGMT confers less resistance to chemotherapeutic alkylating agents, thus increasing treatment efficacy. Currently, there is no extensive examination of the role of MGMT expression in neuroendocrine tumors. We undertook immunohistochemical study of MGMT expression in gastrointestinal (GI) and pancreatic neuroendocrine biopsy and resection specimens.
Design: Search of the patient electronic medical record identified 116 patients over the past five years with neuroendocrine tumors for which paraffin blocks were available. From these, seventy GI tract and pancreatic neuroendocrine tumor specimens (from 69 patients) were retrieved. Immunohistochemical staining was performed using the MGMT antibody and slides were reviewed by two pathologists. Low MGMT expression was defined as IHC intensity of 1 or overall staining present in 50% or less of the tumor cells. High MGMT expression was defined as IHC intensity of 2 or 3 and overall staining greater than 50%. Patient demographic and outcome data was extracted from the electronic medical record and analyzed.
Results: Of the 70 specimens, 65 had evaluable MGMT IHC staining. Low MGMT expression was seen in 35 of 65 cases (54%) and was not significantly associated with age, sex, or race. Recurrence was present in 9 of the low expression cases versus 2 of the high expression cases (p=0.021). Cases with tumor stage of 4 trended toward lower expression, but results were not statistically significant (p =0.066). Tumor grade and presence of metastases were not significantly associated with MGMT expression.
Conclusions: These results suggest that loss of MGMT expression may be associated with more aggressive neuroendocrine tumors of the GI tract and pancreas. Though recurrence was the only characteristic that had a significant association with MGMT expression, higher tumor grade, tumor stage greater than 1, and presence of metastases were all more common in cases with lower MGMT expression. This may reach statistical significance with a greater number of cases. Further studies including analysis of tumors from other sites and correlation with MGMT methylation status are needed.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 116, Tuesday Afternoon