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Prognostic molecular biomarkers in endometrial cancer: A review.

ABSTRACT:

Background

Endometrial cancer (EC) is the fourth most common malignancy in women worldwide and the most common gynecological cancer in developed countries. The endometrioid subtype has an excellent prognosis with conventional treatment; however, recurrence reduces overall survival.

Objective

Describe the most relevant evidence regarding selected potential molecular biomarkers that may predict overall survival (OS), relapse-free survival (RFS), and cancer-specific survival (CSS) in EC.

Methods

An exhaustive search was performed in PUBMED with the search terms endometrial cancer, molecular biomarker, and survival. We selected original articles written in English about endometrial cancer, molecular biomarkers, and that included survival analysis published between January 2000 and December 2016.

Results

Several molecular prognostic biomarkers have been studied in terms of survival and therapeutic response in women with endometrial cancer; hormone receptors, microRNAs, and other molecules have emerged as potentially useful biomarkers, including HER2, p21, HE4, PTEN, p27, ANCCA, and ANXA2.

Conclusions

The use of biomarkers in the assessment of OS, RFS, and CSS requires large trials to expand our understanding of endometrial carcinogenesis. Several molecular markers are significantly associated with a high tumor grade and advanced clinical stage in EC and, therefore, could have additive effects when combined.

SUBMITTER: Hernandez JE

PROVIDER: S-EPMC8315102 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundClinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer.MethodsThis was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-ϵ (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses.ResultsAge >65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the "no specific molecular profile" (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1‒136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup.ConclusionsThe prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.