Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies

Abstract

Background: When determining adjuvant treatment for endometrial cancer, the decision typically relies on factors such as cancer stage, histologic grade, subtype, and a few histopathologic markers. The Cancer Genome Atlas revealed molecular subtyping of endometrial cancer, which can provide more accurate prognostic information and guide personalized treatment plans.

Objective: To summarize the expression and molecular basis of the main biomarkers of endometrial cancer.

Search strategy: PubMed was searched from January 2000 to March 2023.

Selection criteria: Studies evaluating molecular subtypes of endometrial cancer and implications for adjuvant treatment strategies.

Data collection and analysis: Three authors independently performed a comprehensive literature search, collected and extracted data, and assessed the methodological quality of the included studies.

Main results: We summarized the molecular subtyping of endometrial cancer, including mismatch repair deficient, high microsatellite instability, polymerase epsilon (POLE) exonuclease domain mutated, TP53 gene mutation, and non-specific molecular spectrum. We also summarized planned and ongoing clinical trials and common therapy methods in endometrial cancer. POLE mutated endometrial cancer consistently exhibits favorable patient outcomes, regardless of adjuvant therapy. Genomic similarities between p53 abnormality endometrial cancer and high-grade serous ovarian cancer suggested possible overlapping treatment strategies. High levels of immune checkpoint molecules, such as programmed cell death 1 and programmed cell death 1 ligand 1 can counterbalance mismatch repair deficient endometrial cancer immune phenotype. Hormonal treatment is an appealing option for high-risk non-specific molecular spectrum endometrial cancers, which are typically endometrioid and hormone receptor positive. Combining clinical and pathologic characteristics to guide treatment decisions for patients, including concurrent radiochemotherapy, chemotherapy, inhibitor therapy, endocrine therapy, and immunotherapy, might improve the management of endometrial cancer and provide more effective treatment options for patients.

Conclusions: We have characterized the molecular subtypes of endometrial cancer and discuss their value in terms of a patient-tailored therapy in order to prevent significant under- or overtreatment.

Keywords: TP53 gene mutation; defective mismatch repair; endometrial cancer; microsatellite instability; non-specific molecular spectrum; polymerase epsilon exonuclease domain mutated.