ArticleWorld journal of surgery2025
Loss of O6-Methylguanine-DNA Methyltransferase Protein Expression by Immunohistochemistry Is Associated With Response to Capecitabine and Temozolomide in Neuroendocrine Neoplasms.
Article in World journal of surgery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Systemic therapy for gastroenteropancreatic neuroendocrine neoplasms: current landscape and future directions.Therapeutic advances in medical oncology · 2026Review
- Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA recent prospective phase II study (ECOG-ACRIN E2211) demonstrated that MGMT deficiency was associated with a significant response to capecitabine and temozolomide (CAPTEM) in pancreatic neuroendocrine neoplasms (NENs); however, routine MGMT analysis in NENs was not recommended. Our study sought to demonstrate whether loss of MGMT protein expression is associated with improved overall survival (OS) in patients receiving CAPTEM for NENs from various tumor sites. MATERIALS AND
methodsParaffin-embedded tumor samples were evaluated by immunohistochemistry (IHC) using an MGMT monoclonal antibody. Intact MGMT protein expression (i.e., IHC positivity) was defined as any staining intensity (> 1+) in ≥ 36% of neoplastic cells according to an internal validation study. IHC and pyrosequencing for MGMT promotor methylation was performed in an independent cohort of 58 NENs. Real-world OS was extrapolated from insurance claims data with Kaplan-Meier estimates from the date of first CAPTEM administration to the last date of contact.
resultsThe study cohort included 80 patients (42 men and 38 women) with a median age of 57 years (range: 19-89). They had various NENs (33 pancreatic, 17 intestinal, 7 pulmonary, 8 other, and 15 of unknown origin) treated with CAPTEM. The median OS for the 48 patients with MGMT negative tumors was 31 months compared to 17.5 months for the 32 patients whose tumors were MGMT positive by IHC (HR: 1.75 [95% CI: 1.066-2.87] and p = 0.025). IHC results from the independent cohort of 58 NENs showed only 57% concordance with pyrosequencing results.
conclusionsMGMT promotor status by IHC may be a clinically useful indicator that predicts improved OS for NENs treated with CAPTEM, but IHC does not reliably correlate with the findings of MGMT promoter methylation by pyrosequencing.
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