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Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX

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Abstract

Background

To date, no predictive biomarker for the efficacy of FOLFIRINOX in metastatic pancreatic adenocarcinoma has been demonstrated. Deficiency in O6-methylguanine-DNA methyltransferase (MGMT) has been associated with a therapeutic response in endocrine tumors of the pancreas and the lack of expression of protein 53 (p53) could interfere with the action of MGMT.

Objective

The aim of our study was to assess the prevalence of MGMT and p53 in patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX as a first-line treatment and to investigate their association with therapeutic response and survival.

Patients and Methods

The immunohistochemical expression of MGMT was recorded as present or absent and the expression of p53 was semi-quantitatively scored in 30 patients with metastatic pancreatic adenocarcinoma, at Angers Hospital in France between September 2011 and June 2015. Clinical and radiologic data were collected retrospectively.

Results

The presence or absence of MGMT expression entailed no significant differences in response rate. Median values of progression-free survival (PFS) and overall survival (OS) were lower in patients with MGMT expression, but sample size is too small to conclude that there is a statistically significant difference. No significant relationship for response rate and PFS was observed in relation with p53 expression. By contrast, patients with a strong tumor expression of p53 had a significantly lower OS compared to patients with no or weak expression of the protein (p = 0.027). There was a positive correlation between the expression of p53 and MGMT (p = 0.08).

Conclusions

These preliminary findings suggest that for patients treated with FOLFIRINOX as a first-line treatment for metastatic pancreatic adenocarcinoma, the immunohistochemical evaluation of MGMT could not predict the clinical outcome; however, the survival was not significant probably because of the under-powered study (due to small sample size). A strong tumor expression of p53 is associated with a poor prognosis of OS.

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Authors and Affiliations

  1. Department of Gastroenterology, University Hospital Centre, Angers, France

    Carole Vitellius, Dominique Luet, Fanny Foubert & François-Xavier Caroli-Bosc

  2. Department of Anatomic pathology, University Hospital Centre, Angers, France

    Caroline Eymerit-Morin & Marie-Christine Rousselet

  3. Laboratory HIFIH, UFR Santé, Angers, France

    Lionel Fizanne, Sandrine Bertrais & François-Xavier Caroli-Bosc

Authors
  1. Carole Vitellius
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  2. Caroline Eymerit-Morin
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  3. Dominique Luet
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  4. Lionel Fizanne
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  5. Fanny Foubert
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  6. Sandrine Bertrais
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  7. Marie-Christine Rousselet
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  8. François-Xavier Caroli-Bosc
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Corresponding author

Correspondence to Carole Vitellius.

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Funding

No source of funding was used to conduct this study.

Conflict of interest

Carole Vitellius, Caroline Eymerit-Morin, Dominique Luet, Lionel Fizanne, Fanny Foubert, Sandrine Bertrais, Marie-Christine Rousselet and François-Xavier Caroli-Bosc have no conflict of interest.

Ethics approval

Our study has been approved by Ethical committee of Angers hospital (Number 2016/123).

Informed consent

Informed consents of patients were not required (majority of patients died).

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Vitellius, C., Eymerit-Morin, C., Luet, D. et al. Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX. Clin Drug Investig 37, 669–677 (2017). https://doi.org/10.1007/s40261-017-0522-3

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  • DOI: https://doi.org/10.1007/s40261-017-0522-3

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