Molecular testing for endometrial cancer: An SGO clinical practice statement

• Published in: Gynecologic oncology Vol. 168; pp. 48 - 55
• Main Authors: Walsh, Christine S., Hacker, Kari E., Secord, Angeles Alvarez, DeLair, Deborah F., McCourt, Carolyn, Urban, Renata
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2023
• Subjects: Biomarkers; Biomarkers, Tumor - genetics; Endometrial cancer; Endometrial Neoplasms - diagnosis; Endometrial Neoplasms - genetics; Endometrial Neoplasms - therapy; Female; Humans; Mismatch repair deficiency; Molecular Diagnostic Techniques; Molecular testing; Mutation; P53; POLE; Prognosis; Tumor Suppressor Protein p53 - genetics; Biomarkers; Molecular testing; Mismatch repair deficiency; Endometrial cancer; POLE; P53
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2022.10.024

The Cancer Genome Atlas publication first described the genomic landscape of endometrial cancer and characterized these cancers into four molecular subtypes with different prognoses. The Proactive Molecular Classifier for Endometrial Cancer was developed to more easily and inexpensively classify endometrial cancers into four similar molecular subtypes which are termed POLE, mismatch repair deficient, p53 abnormal and no specific molecular profile. Beyond these four subtypes, other molecular biomarkers may influence clinical behavior and response to targeted therapies and include beta-catenin, Her2 amplification, PI3K/mTOR/AKT alterations, L1CAM, hormone receptor expression, tumor mutational burden, and ARID1A. There are numerous clinical trials exploring treatment escalation and de-escalation within the four molecular subtypes as well as matching targeted therapies to specific mutational or biomarker profiles. All endometrial cancers should undergo basic molecular classification that includes assessment of mismatch repair status. POLE and p53 status are prognostic and may become actionable in the future. Clinicians who treat patients with endometrial cancer should understand the role of molecular classification in guiding treatment. The goal of this practice statement is to guide appropriate testing, interpretation, and application of molecular information in endometrial cancer.
•Endometrial cancer is increasingly classified by molecular subtypes and biomarkers that impact prognosis and treatment.•The Cancer Genome Atlas and the ProMisE algorithm define four molecular subtypes of endometrial cancer.•Various testing strategies can be used to identify endometrial cancer biomarkers.•Endometrial cancer treatment paradigms are impacted by molecular classification and ongoing clinical trials are biomarker-driven.