Frequency of Known Translocations Detected by Fluorescence In Situ Hybridization in Endometrial and Endometrioid Stromal Tumors (ESTs): A Study of 57 Patients.
Sarah Chiang, Rola Ali, Cheng-Han Lee, Blake Gilks, Esther Oliva. Massachusetts General Hospital, Boston; BC Cancer Agency, Vancouver, BC, Canada
Background: Translocations resulting in gene fusion are often seen in ESTs, particularly endometrial stromal nodules (ESNs) and low-grade endometrial stromal sarcomas (ESSs). While JAZF1-JJAZ1 gene fusion is most common, EPC1-PHF1 and JAZF1-PHF1 gene fusions have been rarely reported. Translocations have not been reported in ovarian endometrioid stromal sarcomas (Ov-ESS). We investigated the frequency of rearrangements involving JAZF1, JJAZ1, EPC1, and PHF1 in ESTs and Ov-ESS and correlated molecular and histologic findings.
Design: 57 patients were included. A tissue microarray was made from 62 tumors, including 19 ESNs, 27 primary ESSs, 14 metastatic ESSs, and 2 Ov-ESSs. Of these tumors, 5 and 2 metastatic ESSs samples belonged to one patient each respectively (primary tumor not available). Variant histologic patterns, including smooth muscle (7), fibrous and/or myxoid (7), sex-cord (6), glandular (3), epithelioid (1), skeletal muscle (1), and fatty (1) differentiation were seen in 7 ESNs, 10 primary ESSs, and 6 metastatic ESSs. FISH was performed on all tissue microarray samples using break-apart and fusion probes for JAZF1, JJAZ1, EPC1, and PHF1 genes.
Results: FISH was successful in 51 samples. Rearrangements of JAZF1, JJAZ1, EPC1, or PHF1 were detected in 31 tumors (61%), including 10/14 ESNs (71%), 12/23 primary ESSs (52%), 7/12 metastatic ESSs (58%), and 2/2 Ov-ESS (100%) of classic (78%) and variant morphology (35%). JAZF1-JJAZ1 gene fusion was found in 21 (68%), including 9 ESNs, 9 primary ESSs, 2 metastatic ESSs, and 1 Ov-ESS. JAZF1-PHF1 gene fusion was found in 1 primary ESS (<1%); EPC1-PHF1 gene fusion in 1 primary ESS and 1 metastatic ESS (1%). 7 cases showed rearrangements of JAZF1 and PHF1 with no apparent fusion partner. Gene rearrangement status in patients with multiple metastatic ESSs remained unchanged. Translocations were not detected in 20 cases. No correlation was found between different translocations and morphology of tumors.
Conclusions: Our results confirm that translocations are present in many ESTs and can be seen in Ov-ESS. JAZF1-JJAZ1 gene fusion is the most common rearrangement, but EPC1-PHF1 and JAZF1-PHF1 gene fusions can rarely be found. Of note, JAZF1 and PHF1 appear to have fusion partners which have yet to be identified. Although no apparent correlation between morphology and specific gene rearrangements was found, gene fusions are more common in tumors of classic morphology than EST variants.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 8:45 AM
Platform Session: Section D, Tuesday Morning