[1183] Cyclin D1 Is a Sensitive and Specific Diagnostic Immunomarker for YWHAE-FAM22A/B Endometrial Stromal Sarcoma

Cheng-Han Lee, Rola Ali, Adrian Marino-Enriquez, Wen-bin Ou, Meijun Zhu, Xiangqian Guo, Allayne L Brunner, Sarah Chiang, Esther Oliva, Marjan Rouzbahman, C Blake Gilks, Paola Dal Cin, Rob B West, Matt van de Rijn, Jonathan A Fletcher, Marisa R Nucci. Vancouver General Hospital, Vancouver, Canada; Brigham and Women's Hospital, Boston; Stanford University Medical Center, Stanford; Massachusetts General Hospital, Vancouver; Toronto General Hospital, Toronto, Canada

Background: We recently described a novel genetic fusion YWHAE-FAM22A/B resulting from translocation t(10;17)(q22;p13) in a subset of endometrial stromal sarcomas (ESS) which are histologically higher-grade and clinically more aggressive than JAZF1-rearranged ESS. We describe here the utility of cyclin D1 as a diagnostic immunomarker for YWHAE-FAM22A/B ESS.
Design: Gene expression profiling was performed by 3' end sequencing in 3 YWHAE-FAM22A/B ESS, 4 JAZF1 ESS and 4 uterine leiomyosarcomas. Significance analysis of microarray data was used to identify genes (immunomarkers) substantially upregulated in YWHAE-FAM22A/B ESS. Immunomarker specificity and sensitivity were evaluated in a series of YWHEA-FAM22A/B ESS and other uterine tumors.
Results: The 3' end sequencing profiles demonstrated cyclin D1 overexpression in YWHAE-FAM22A/B ESS compared to JAZF1 ESS and leiomyosarcomas: this candidate immunomarker was selected for further evaluation because of its general availability in pathology laboratories. Immunohistochemically, > 70% of nuclei in the round cell/epithelioid cell component of all YWHAE-FAM22A/B ESS (N = 10) demonstrated diffuse moderate-to-strong nuclear cyclin D1 staining (comparable to that seen in Mantle cell lymphoma) and such diffuse positivity was rarely seen (0.4%) in other uterine tumors (Table 1). Other than YWHAE-FAM22A/B ESS, most uterine sarcomas (98%) displayed cyclin D1 straining in < 20% of tumor nuclei.

Cyclin D1 (Thermoscientific) immunostaining results in 267 uterine tumors.
 Number of cases examinedCyclin D1 positive cases (>70% moderate-strong nuclear positivity)
ESS with JAZF1/SUZ12/PHF1/EPC1 rearrangement340 (0%)
ESS with YWHAE-FAM22A/B rearrangement1010 (100%)
Sarcoma NOS120 (0%)
Adenosarcoma*250 (0%)
Leiomyosarcoma1111 (1%)
Malignant mixed mullerian tumor140 (0%)
Leiomyoma490 (0%)
Endometrial stromal nodule30 (0%)
Polypoid endometriosis70 (0%)
Uterine tumors resembling ovarian sex cord tumor (UTROSCT)20 (0%)
* 8 cases showed sarcomatous overgrowth

Conclusions: We have identified a cyclin D1 as a sensitive and specific diagnostic immunomarker for YWHAE-FAM22A/B ESS. When evaluating uterine sarcomas where the differential of ESS with high grade histologic features is considered, cyclin D1 should be included in the immunohistochemical work-up to evaluate the possibility of YWHAE-FAM22A/B ESS.
Category: Gynecologic & Obstetrics

Monday, March 19, 2012 11:30 AM

Platform Session: Section E, Monday Morning


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