[1096] Genetic Reclassification of Undifferentiated Endometrial Sarcoma: Clinical Relevance

Rola H Ali, Shuichi Kurihara, Makoto Endo, Marjan Rouzbahman, Lien N Hoang, Nataliya Melnyk, Adrian Marino-Enriquez, Paola Dal Cin, Jonathan A Fletcher, Esther Oliva, David G Huntsman, Yoshinao Oda, Marisa R Nucci, Cheng-Han Lee. University of British Columbia, Vancouver, Canada; Kyushu University, Fukuoka, Japan; University of Toronto, Toronto, Canada; Brigham and Women's Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; British Columbia Cancer Agency, Vancouver, Canada

Background: Undifferentiated endometrial sarcoma (UES) is the current designation for tumors formerly considered as high-grade endometrial stromal sarcoma (ESS). Some UES exhibit uniform nuclear features (UES-U) whereas others exhibit nuclear pleomorphism (UES-P). We recently identified YWHAE-FAM22 genetic rearrangement in tumors diagnosed as UES or high-grade ESS. YWHAE-FAM22 tumors are clinically more aggressive than low-grade ESS with JAZF1-SUZ12 genetic rearrangement, but it is yet unclear whether YWHAE-FAM22 tumors differ in clinical course from UES lacking YWHAE-FAM22.
Design: We employed YWHAE-FAM22 split-apart fluorescence in situ hybridization and RT-PCR assays to genetically classify 50 UES/high-grade ESS as YWHAE-FAM22 ESS vs. YWHAE-FAM22-negative UES (UES-U and UES-P).
Results: Of the 50 tumors, 12 showed appreciable nuclear pleomorphism at 40x magnification (UES-P) and none of these had YWHAE-FAM22 rearrangement. Among the 38 tumors with uniform nuclear features, 24 had YWHAE-FAM22 rearrangement (YWHAE-FAM22 ESS), including 12 with focal low-grade component that mimicked classic low-grade ESS. The remaining 14 cases with uniform nuclear features lacked apparent YWHAE-FAM22 rearrangement (UES-U). The clinical features are shown in Table 1 with the result of Kaplan-Meier analysis shown in Figure 1.

Table 1
Age (average +/- SE)46 +/- 355 +/-560 +/-3
FIGO (1988) stage   
16 (27%)5 (42%)5 (45%)
2-416 (73%)7 (58%)6 (55%)
Follow-up (with >1 year)   
Died of disease6 (32%)7 (58%)8 (80%)
Alive with disease8 (42%)2 (17%)0
Alive with no disease5 (26%)3 (25%)2 (20%)
Adjuvant therapy   
Chemotherapy and/or radiation12 (75%)11 (84%)10 (91%)
None4 (25%)2 (16%)1 (9%)

Conclusions: Due to the high-grade nuclear features present, YWHAE-FAM22 ESS is frequently classified as UES. Our findings suggest that YWHAE-FAM22 ESS is associated with a better prognosis than UES and it is therefore important to distinguish YWHAE-FAM22 ESS from UES.
Category: Gynecologic & Obstetrics

Tuesday, March 5, 2013 11:15 AM

Proffered Papers: Section E, Tuesday Morning


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