The Molecular Changes and Genetic Pathways of the Endometrial Precancers
Keywords:
Endometrial hyperplasia, atypical hyperplasia / endometrioid intraepithelial neoplasia, genetic mutationsAbstract
Background: Endometrial hyperplasia (EH) is considered as precursor lesion to endometrioid endometrial cancer. The recently updated 2020 World Health Organization (WHO) distinguishes between atypical hyperplasia / endometrioid intraepithelial neoplasia (AH/EIN) and endometrial hyperplasia without atypia. AH/EIN is with higher risk for progression to EC than EH without atypia. The progression of atypical endometrial hyperplasia to endometrial cancer is driven by a series of molecular and genetic alterations. Recent studies focused on genetic association between AH/EIN and EC, especially in the context of molecular classification. The most common genetic mutations that occur in AH/EIN and EC are MSI, PTEN, CTNNB1, ARID1A, PIK3CA, KRAS, and PAX2.
Aim: The work aimed to give an overview on the molecular changes and genetic pathways of the endometrial precancers and the role of it in progression and diagnosis of EC.
Conclusion and Future directions: Our knowledge of endometrial carcinoma and associated precancers has greatly improved as a result of the notable advancements in genomic, molecular, and biomarker research. The development of diagnostic schemas during the previous 20 years reflects this progress. The incorporation of biomarkers into our daily clinical practice has been a gradual but steady process, leading to the updated diagnostic criteria in WHO 2020. There are genetic association between AH/EIN and EC, especially in the context of molecular classification. The most common genetic mutations that occur in AH/EIN and EC are MSI, PTEN, CTNNB1, ARID1A, PIK3CA, KRAS, and PAX2. Rapid advancements in our knowledge of the molecular pathways and abnormalities that define early endometrial cancers, precancers, and precursors should be used consistently to improve risk stratification and diagnostic approaches for this prevalent premalignancy in women. However, problems still exist and need to be investigated further in subsequent research.