Frequency of Known Gene Rearrangements in Endometrial Stromal Tumors

Translocations resulting in gene fusion are characteristic of endometrial stromal tumors (ESTs). Rearrangements of JAZF1, SUZ12, PHF1, and EPC1 have been reported in endometrial stromal nodules (ESNs), endometrial stromal sarcomas (ESSs), and rarely in undifferentiated endometrial sarcomas (UESs). Detection of JAZF1, SUZ12, EPC1, and PHF1 rearrangement by fluorescence in situ hybridization was performed on tissue microarrays consisting of 94 ESTs of classic and variant morphology (20 ESNs, 43 primary uterine ESSs, 15 metastatic uterine ESSs, 4 primary extrauterine ESSs, 7 primary uterine UESs, and 5 unclassified ESTs), 16 Müllerian adenosarcomas, 2 malignant mixed Müllerian tumors, 2 uterine tumors resembling ovarian sex-cord tumors, 2 highly cellular leiomyomas, 1 leiomyosarcoma, and 7 polypoid endometriosis. Rearrangements were detected in 42 of 78 (54%) uterine ESTs, with JAZF1-SUZ12 fusion found in 50% of ESNs and in 33% of ESSs and JAZF1-PHF1 and EPC1-PHF1 fusions found in 1% and <1% of ESSs, respectively. PHF1 and JAZF1 were rearranged with unknown partners in 8 uterine ESTs. JAZF1-SUZ12 fusion, EPC1-PHF1 fusion, and PHF1 rearrangement were found in 3 extrauterine ESSs, whereas no rearrangements were observed in UESs or in any other non-EST studied. Our data confirm that gene rearrangements are present in more than 50% of uterine ESTs, with JAZF1-SUZ12 fusion being the most common, followed by rare EPC1-PHF1 and JAZF1-PHF1 fusions. The presence of identical gene rearrangements in both uterine and extrauterine ESTs suggests a similar pathogenesis. The presence of detectable gene rearrangements in uterine ESS may predict better patient outcome.