Serial genomic analysis of endometrium supports the existence of histologically indistinct endometrial cancer precursors.

Autor: Aguilar M; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Zhang H; Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA., Zhang M; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Cantarell B; Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Sahoo SS; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Li HD; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Cuevas IC; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Lea J; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Miller DS; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Chen H; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Zheng W; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Gagan J; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Lucas E; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Castrillon DH; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2021 May; Vol. 254 (1), pp. 20-30. Date of Electronic Publication: 2021 Mar 09.
DOI: 10.1002/path.5628
Abstrakt: The endometrium is unique as an accessible anatomic location that can be repeatedly biopsied and where diagnostic biopsies do not extirpate neoplastic lesions. We exploited these features to retrospectively characterize serial genomic alterations along the precancer/cancer continuum in individual women. Cases were selected based on (1) endometrial cancer diagnosis/hysterectomy and (2) preceding serial endometrial biopsies including for some patients an early biopsy before a precancer histologic diagnosis. A comprehensive panel was designed for endometrial cancer genes. Formalin-fixed, paraffin-embedded specimens for each cancer, preceding biopsies, and matched germline samples were subjected to barcoded high-throughput sequencing to identify mutations and track their origin and allelic frequency progression. In total, 92 samples from 21 patients were analyzed, providing an opportunity for new insights into early endometrial cancer progression. Definitive invasive endometrial cancers exhibited expected mutational spectra, and canonical driver mutations were detectable in preceding biopsies. Notably, ≥1 cancer mutations were detected prior to the histopathologic diagnosis of an endometrial precancer in the majority of patients. In 18/21 cases, ≥1 mutations were confirmed by abnormal protein levels or subcellular localization by immunohistochemistry, confirming genomic data and providing unique views of histologic correlates. In 19 control endometria, mutation counts were lower, with a lack of canonical endometrial cancer hotspot mutations. Our study documents the existence of endometrial lesions that are histologically indistinct but are bona fide endometrial cancer precursors. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
(© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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