domingo, 19 de noviembre de 2017

An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer. - PubMed - NCBI

2017 Nov 10. pii: S0090-8258(17)31459-2. doi: 10.1016/j.ygyno.2017.10.037. [Epub ahead of print]

An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer.

Cosgrove CM1, Tritchler DL2, Cohn DE1, Mutch DG3, Rush CM1, Lankes HA4, Creasman WT5, Miller DS6, Ramirez NC4, Geller MA7, Powell MA3, Backes FJ1, Landrum LM8, Timmers C1, Suarez AA1, Zaino RJ9, Pearl ML10, DiSilvestro PA11, Lele SB12, Goodfellow PJ13.

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Abstract

OBJECTIVES:

The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification.

METHODS:

Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods.

RESULTS:

Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status.

CONCLUSIONS:

A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system.