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Endocr Relat Cancer. 2016 Aug;23(8):625-33. doi: 10.1530/ERC-16-0117. Epub 2016 Jun 28.

MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

Author information

1
Department of PathologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France U1149 - University Paris DiderotParis, France.
2
Department of Gastroenterology and PancreatologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France.
3
U1149 - University Paris DiderotParis, France Department of Gastroenterology and PancreatologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France.
4
Department of RadiologyAP-HP, DHU UNITY, Beaujon Hospital, Clichy, France.
5
Department of PathologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France.
6
Department of Somatic GeneticAP-HP, DHU UNITY, Bichat University Hospital, Paris, France.
7
Methodology and Quality of Life in Oncology Unit (EA 3181)University Hospital of Besançon, Besançon, France.
8
U1149 - University Paris DiderotParis, France Department of Digestive OncologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France.
9
U1149 - University Paris DiderotParis, France Department of PathologyAP-HP, DHU UNITY, Bichat University Hospital, Paris, France anne.couvelard@bch.aphp.fr.

Abstract

Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

KEYWORDS:

MGMT; methylation; pancreatic neuroendocrine tumors; temozolomide

PMID:
27353036
DOI:
10.1530/ERC-16-0117
[Indexed for MEDLINE]

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