Skill Checkup: A Woman With Increasing Abdominal Pain, Nausea, Vomiting, and Ascites

Pamela Soliman, MD, MPH


April 21, 2022

Molecular analysis has classified endometrial carcinoma into four clinically significant molecular subgroups with varying prognoses: POLE mutations, MSI-H, CN low, and CN high.

Patients with POLE mutational status have a favorable prognosis. POLE-mutant tumors are defined by hot spot mutations in the exonuclease domain of DNA POLE. They have significantly improved progression-free survival, regardless of histotype and grade.

CN-low tumors are typically low-grade endometrioid carcinomas. They frequently harbor mutations in PTEN, PIK3CA, ARID1A, CTNNB1, and KRAS. On the other hand, CN-high tumors are associated with the poorest outcome of endometrial cancers, consisting of serous carcinomas and some high-grade endometrioid carcinomas. These tumors have extensive CN alterations, frequent mutations in TP53, few DNA methylation changes, and low estrogen receptor (ER)/progesterone (PR) receptor levels.

Finally, MSI-high tumors can be either low-grade or high-grade endometrioid carcinomas.

In terms of risk factors of developing uterine neoplasms, these features include early age at menarche, nulliparity, late age at menopause, Lynch syndrome, being ≥ 55 years of age, and tamoxifen use. Increased levels of estrogen, which may be caused by obesity, diabetes, and a high-fat diet, is another risk factor.


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