Matt van de Rijn

Publication Details

  • Cyclin D1 as a Diagnostic Immunomarker for Endometrial Stromal Sarcoma With YWHAE-FAM22 Rearrangement AMERICAN JOURNAL OF SURGICAL PATHOLOGY Lee, C., Ali, R. H., Rouzbahman, M., Marino-Enriquez, A., Zhu, M., Guo, X., Brunner, A. L., Chiang, S., Leung, S., Nelnyk, N., Huntsman, D. G., Gilks, C. B., Nielsen, T. O., Dal Cin, P., van de Rijn, M., Oliva, E., Fletcher, J. A., Nucci, M. R. 2012; 36 (10): 1562-1570

    Abstract:

    Endometrial stromal sarcoma (ESS) characterized by YWHAE-FAM22 genetic fusion is histologically higher grade and clinically more aggressive than ESS with JAZF1-SUZ12 or equivalent genetic rearrangements, hence it is clinically important to recognize this subset of ESS. To identify diagnostic immunomarkers for this biologically defined ESS subset, we compared gene expression profiles between YWHAE-FAM22 ESS and JAZF1-rearranged ESS. These studies showed consistent upregulation of cyclin D1 in YWHAE-FAM22 ESS compared with JAZF1-SUZ12 ESS. Immunohistochemically, the high-grade round cell component of all 12 YWHAE-FAM22 ESS demonstrated diffuse (?70%) moderate to strong nuclear cyclin D1 staining, and this diffuse positivity was not seen in 34 ESSs with JAZF1 and equivalent genetic rearrangements or in 21 low-grade ESS with no demonstrable genetic rearrangements. In a series of 243 non-ESS pure uterine mesenchymal and mixed epithelial-mesenchymal tumors, only 2 of 8 undifferentiated endometrial sarcomas with nuclear uniformity and 1 of 80 uterine leiomyosarcomas demonstrate diffuse cyclin D1 immunoreactivity. Both cyclin D1-positive undifferentiated endometrial sarcomas showed diffuse strong CD10 staining, which is consistently absent in the high-grade round cell component of YWHAE-FAM22 ESS. The low-grade spindle cell component of YWHAE-FAM22 ESS showed a spatially heterogenous cyclin D1 staining pattern that was weaker and less diffuse overall. Our findings indicate that cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22 ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS.

    View details for DOI 10.1097/PAS.0b013e31825fa931

    View details for Web of Science ID 000309115100018

    View details for PubMedID 22982899

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