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Br J Cancer. 2016 Jun 14;114(12):1387-94. doi: 10.1038/bjc.2016.144. Epub 2016 May 24.

Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection.

Author information

1
Department of Medical Oncology, Institut Curie, René Huguenin Hospital, 35 rue Dailly, 92210 Saint-Cloud, France.
2
Pharmacogenomics Unit, Department of Genetics, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
3
Center of Oncology, University Hospital of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
4
Department of Surgical Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
5
Department of Radiation Oncology, Institut Curie, Reneé Huguenin Hospital, 35 rue Dailly, 92210 Saint-Cloud, France.
6
Department of Medical Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
7
Translational Research, Research Center, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
8
IFR71, Faculty of Biologic and Pharmacologic Sciences, University Paris Descartes, Sorbonne Paris Cité, Paris, France.
9
Department of Pathology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
10
Department of Radiation Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
11
Department of Public Health, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
12
Department of Gastroenterology, University Hospital of Rennes, University of Rennes 1, Rennes, France.

Abstract

BACKGROUND:

A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment.

METHODS:

We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis.

RESULTS:

Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P=0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n=38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P=0.048), gender (P=0.045) and PIK3CA mutation (P=0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P=0.025).

CONCLUSIONS:

Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients.

PMID:
27219019
PMCID:
PMC4984471
DOI:
10.1038/bjc.2016.144
[Indexed for MEDLINE]
Free PMC Article

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