Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-05

AUTHORS

Cheng-Han Lee, Lien N Hoang, Stephen Yip, Carolina Reyes, Adrian Marino-Enriquez, Grant Eilers, Derrick Tao, Sarah Chiang, Jonathan A Fletcher, Robert A Soslow, Marisa R Nucci, Esther Oliva

ABSTRACT

Endometrial stromal sarcomas with the YWHAE-NUTM2A/B genetic fusion characteristically contain high-grade round to epithelioid cell component that is strongly and diffusely cyclin D1-positive and it may or may not show an associated low-grade fibroblastic/myxoid cell component. They are clinically more aggressive than endometrial stromal sarcomas with the JAZF1-SUZ12 genetic fusion and frequently demonstrate extrauterine extension at initial clinical presentation. In this setting, the tumor may be misdiagnosed as gastrointestinal stromal tumor. This study examines the expression of KIT and ANO1 in 14 YWHAE-NUTM2A/B tumors by immunohistochemistry. Staining localization was determined as membranous and/or cytoplasmic, and the staining intensity was assessed (negative, weak, moderate and strong). Of the 14 tumors, 6 contained only a high-grade round cell component, 2 only a low-grade fibroblastic component and 6 had both components in the slides evaluated. The high-grade round cell component displayed moderate to strong membranous/cytoplasmic KIT staining in all tumors (12 of 12). The low-grade fibroblastic cell component showed only weak cytoplasmic KIT staining in 3 of 8 tumors. In contrast, ANO1 was negative in all 14 neoplasms, irrespective of the component evaluated. Sanger sequencing analysis (exons 9, 11, 13 and 17) and Ampliseq Cancer Panel mutation screen (Ion Torrent) demonstrated no KIT mutations in three KIT-positive YWHAE-NUTM2A/B tumors. This study shows that the high-grade round cell component of YWHAE-NUTM2A/B endometrial stromal sarcoma consistently expresses KIT but lacks KIT hotspot mutations. KIT expression may represent a potential diagnostic pitfall in the evaluation of YWHAE-NUTM2A/B endometrial stromal sarcoma presenting with pelvic/abdominal mass, particularly in situations where its uterine origin is not definitive, and thus a panel of antibodies that includes ANO1 and cyclin D1 is necessary. More... »

PAGES

751

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2013.199

DOI

http://dx.doi.org/10.1038/modpathol.2013.199

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039250429

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24186140


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