YWHAE Rearrangement Identified by FISH in a Series of Undifferentiated Endometrial Stromal Sarcomas: Genetic and Pathological Correlations
Sabrina Croce, Frederic Chibon, Agnes Ribeiro, Rachel Jacquemart, Louise Jeammet, Marie Sire, Jean-Michel Coindre, Gaetan MacGrogan. Institut Bergonie, Bordeaux, France
Background: Endometrial Stromal tumors (EST) of the uterus represent less than 10% of all uterine mesenchymal tumors. Undifferentiated Stromal Sarcomas (U-ESS) are aggressive malignant tumors with moderate to marked cytological atypia and little resemblance to proliferative-phase endometrial stroma. Unlike ESS, U-ESS doesn't generally harbor a JAZF1/JJAZ1 chromosomal rearrangement. Recently, a rearrangement of (WYHAE) on 17p13 with FAM 22 A-B on chromosome (Chr) arm 10q has been described in U-ESS. The aim of our study was to evaluate the frequency of WYHAE rearrangement and to look for a correlation with morphology.
Design: We collected 29 cases of U-ESS from our Department diagnosed between 1995 and 2011. At the morphological level, we distinguished the U-ESS Uniform (U-ESS-U) and pleiomorphic (U-ESS-P) types according to Kurihara S et al criteria. An immunohistochemical study including CD10, H-caldesmon and desmin was performed. FISH analysis using break-apart probes targeting the WYHAE gene on chr17p13 and JAZF1gene on chr7p15 was performed on paraffin-embedded tissue sections. In-house FISH probes were selected and validated on chromosome spreads.
Results: Mean age at diagnosis was 58.6 years (31 to 93). 22/29 (76%) tumors expressed CD10 marker. Only 2/29(7%) and 2/29(7%) cases showed a weak and heterogeneous positivity for desmin and H-caldesmon, respectively. The tumors expressed estrogen and progesterone receptors in 6/27 (22%) and 8/28 (28%) respectively. FISH was interpretable in 22/29 cases. 9/22 (41%) cases showed a WYHAE chromosomal rearrangement of which 8/9 (89%) showed a uniform morphology (U-ESS-U): 2 with fibromyxoid features, 3 with spindle morphology and 1 with spindle and epithelioid appearance. Only one case (1/9) (11%) showed a pleomorphic morphology (U-ESS-P). No chromosomal rearrangement for JAZF1-JJAZ was detected. Three hybridization profiles were observed: 1 chromosomal rearrangement for YWHAE and 1 normal Chr 17; 1 chromosomal rearrangement for YWHAE and the loss of other Chr 17 and 1 chromosomal rearrangement for YWHAE and a gain of the non-rearranged Chr 17. Never less these tumors showed a very unstable chromosomal profile with loss or gain of part of chromosomes.
Conclusions: YWHAE t(10;17) rearrangement was found in 41% U-ESS in our series and correlated with the uniform, spindle and fibro-myxoid variant.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 11:45 AM
Platform Session: Section E, Monday Morning