Molecular Evaluation of Low-grade Low-stage Endometrial Cancer With and Without Recurrence.

TitleMolecular Evaluation of Low-grade Low-stage Endometrial Cancer With and Without Recurrence.
Publication TypeJournal Article
Year of Publication2021
AuthorsMatrai CE, Ohara K, Eng KWha, Glynn SM, Chandra P, Chatterjee-Paer S, Motanagh S, Mirabelli S, Kurtis B, He B, Sigaras A, Gupta D, Chapman-Davis E, Holcomb K, Sboner A, Elemento O, Ellenson LHedrick, Mosquera JMiguel
JournalInt J Gynecol Pathol
Date Published2021 Sep 06

Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences. Four cases of LGLS EC with recurrence and 8 cases without recurrence were evaluated via whole-exome sequencing. Three of the 4 recurrent tumors were evaluated via Oncomine Comprehensive Assay. The resulting molecular profiles of the primary and recurrent tumors were compared. Two of the 3 recurrent cases showed additional mutations in the recurrence. One recurrent tumor included an additional TP53 mutation and the other recurrent tumor showed POLE and DDR2 kinase gene mutation. The POLE mutation occurred outside the exonuclease domain. PIK3CA mutations were detected in 4 of 4 primary LGLS EC with recurrence and in 3 of 8 disease-free cases. LGLS EC with recurrence showed higher MSIsensor scores compared with LGLS without recurrence. The level of copy number gains in LGLS EC with recurrence was larger than LGLS EC without recurrence. This pilot study showed 1 of 3 recurrent cases gained a mutation associated with genetic instability (TP53) and 1 of them also acquired a mutation in the DDR2 kinase, a potential therapeutic target. We also noted a higher level of copy number gains, MSIsensor scores and PIK3CA mutations in the primary tumors that later recurred.

Alternate JournalInt J Gynecol Pathol
PubMed ID34483300
Related Faculty: 
Andrea Sboner, Ph.D. Juan Miguel Mosquera, M.D.

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