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.
|Age (average +/- SE)||46 +/- 3||55 +/-5||60 +/-3|
|FIGO (1988) stage|
|1||6 (27%)||5 (42%)||5 (45%)|
|2-4||16 (73%)||7 (58%)||6 (55%)|
|Follow-up (with >1 year)|
|Died of disease||6 (32%)||7 (58%)||8 (80%)|
|Alive with disease||8 (42%)||2 (17%)||0|
|Alive with no disease||5 (26%)||3 (25%)||2 (20%)|
|Chemotherapy and/or radiation||12 (75%)||11 (84%)||10 (91%)|
|None||4 (25%)||2 (16%)||1 (9%)|