Short article: Evaluation of O6-methylguanine-DNA methyltransferase as a predicting factor of response to temozolomide-based chemotherapy in well-differentiated metastatic pancreatic neuroendocrine tumors

TitreShort article: Evaluation of O6-methylguanine-DNA methyltransferase as a predicting factor of response to temozolomide-based chemotherapy in well-differentiated metastatic pancreatic neuroendocrine tumors
Type de publicationArticle de revue
AuteurGirot, Paul, Dumars, Clotilde, Mosnier, Jean-François, Muzellec, Léa, Senellart, Hélène, Foubert, Fanny , Caroli-Bosc, François-Xavier , Cauchin, Estelle, Régenet, Nicolas, Matysiak-Budnik, Tamara, Touchefeu, Yann
EditeurLippincott, Williams & Wilkins
TypeArticle scientifique dans une revue à comité de lecture
Année2017
LangueAnglais
DateJuillet 2017
Numéro7
Pagination826-830
Volume29
Titre de la revueEuropean Journal of Gastroenterology & Hepatology
ISSN1473-5687
Mots-clésAdult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Cell Differentiation, Dacarbazine, Disease Progression, Disease-Free Survival, DNA Methylation, DNA Modification Methylases, DNA Repair Enzymes, Female, France, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Male, Middle Aged, Neuroendocrine Tumors, Pancreatic Neoplasms, Patient Selection, Polymerase Chain Reaction, Precision Medicine, Predictive Value of Tests, Promoter Regions, Genetic, Retrospective Studies, Temozolomide, Time Factors, Treatment Outcome, Tumor Suppressor Proteins
Résumé en anglais

OBJECTIVE: Temozolomide (TMZ) is an alkylating agent frequently used in well-differentiated metastatic pancreatic neuroendocrine tumors (PNETs) with very variable responses. O-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose loss of expression has been suggested to be predictive of response to TMZ in various human tumors. We evaluated the predictive value of MGMT status, assessed by immunohistochemistry (IHC) and methylation-specific PCR (MS-PCR), in well-differentiated metastatic PNETs treated by a TMZ-based chemotherapy.

PATIENTS AND METHODS: All patients with metastatic PNETs treated with TMZ-based chemotherapy between 2010 and 2016 in two academic centers, for whom the tumor samples were available, were included. Clinical data were collected and the MGMT status of the tumors was analyzed using MS-PCR and IHC.

RESULTS: Twenty-two patients (nine men, median age 61 years) were included. The loss of MGMT protein expression detected by IHC was observed in 13 (59%) patients and MGMT promoter hypermethylation was detected by MS-PCR in three (15%) out of 20 interpretable cases. MGMT status did not correlate significantly with the best radiological response according to the Response Evaluation Criteria In Solid Tumors criteria or with progression-free survival. There was no correlation between MGMT protein expression and MGMT gene promoter methylation.

CONCLUSION: These results indicate that a deficient MGMT status in PNETs, determined by loss of protein expression in IHC or by the presence of MGMT gene promoter methylation measured by MS-PCR, is not associated with a better response to TMZ-based chemotherapy and cannot be used as a predictive marker to lead treatment decisions.

URL de la noticehttp://okina.univ-angers.fr/publications/ua18976
DOI10.1097/MEG.0000000000000874
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Titre abrégéEur J Gastroenterol Hepatol
Identifiant (ID) PubMed28328619