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J Pathol. 2018 Jul;245(3):265-269. doi: 10.1002/path.5082. Epub 2018 May 2.

Independent development of endometrial epithelium and stroma within the same endometriosis.

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Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Department of Pathology, Seirei Mikatahara Hospital, Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, and the Department of Molecular Pathology, Hiroshima University School of Medicine, Hiroshima, Japan.
Departments of Gynecology and Obstetrics and Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.


The pathogenesis of endometriosis, a common benign but debilitating disease in women, remains elusive. The currently held stem cell theory posits that circulating progenitor/stem cells are deposited outside the uterus, where they differentiate into endometrial stroma and glandular tissue to establish endometriosis. Fundamental to testing this hypothesis is to elucidate the evolution of both tissue types. Here, we applied droplet digital PCR to analyze synonymous and missense somatic passenger mutations, which are neutral with respect to clonal selection, among six non-superficial endometriotic lesions. We found that among 19 mutations sequenced, all were significantly enriched in epithelial but not in stromal components of every lesion examined. Our data indicate that the evolution of non-superficial endometriosis is complex, in that epithelium is clonal and its development is independent of stroma, providing new insight into the genesis of endometriosis. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


DNA; clonal evolution; digital PCR; endometriosis; epithelium; exome; gynecologic disease; pathogenesis; sequence mutations; stem cells; stroma


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