Morphological and molecular-genetic evolution of the endometrial polyp to adenocarcinoma

Atypical endometrial hyperplasia and endometrial adenocarcinoma are successive stages of malignant transformation of the uterine epithelium. Usually genomic instability and tumor mutation burden progressively increase during carcinogenesis. In case of endometrial cancer, the presence of a mutation in the exonuclease domain of the POLE gene and/or a DNA mismatch repair deficiency (dMMR) leads to genomic instability at early stages of tumor development. This paper describes a clinical case of a 49-year-old female patient with synchronous presence of several stages of the endometrium malignant transformation: glandular polyp without signs of atypia, atypical hyperplasia and highly differentiated endometrioid adenocarcinoma. In all substrates, the POLE p.Pro286Arg mutation was detected. In the glandular polyp sample, it was detected with a minimal variant allele frequency (1%). At the same time, in the tissue of atypical hyperplasia and adenocarcinoma, this mutation led to an explosive accumulation of oncogenic genetic variants. This observation indicates role of mutation in the POLE gene as an early driver of carcinogenesis and emphasizes the importance of its determination in atypical endometrial proliferations.