Endometrial Stromal Sarcomas with Sex Cord Differentiation Are Associated with PHF1 Rearrangement
Emanuela D'Angelo, Rola H Ali, Inigo Espinosa, Cheng-Han Lee, David G Huntsman, C Blake Gilks, Jaime Prat. Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research (IIB Sant Pau), Autonomous University of Barcelona, Barcelona, Spain; University of British Columbia, Vancouver, BC, Canada; Centre for Translational and Applied Genomics (CTAG), British Columbia Cancer Agency, Vancouver, BC, Canada
Background: Endometrial stromal tumors (ESTs) may pose diagnostic challenges particularly when they exhibit variant histologic appearances, involve extrauterine sites, or present as metastatic disease. In such cases, immunohistochemical markers as well as identification of specific nonrandom chromosomal rearrangements may be helpful. Over the last decade, fluorescence in situ hybridization (FISH) has been progressively incorporated as a diagnostic tool for the evaluation of ESTs. The purpose of this study was to review a series of these tumors and compare the results of FISH analysis with the clinicopathological characteristics.
Design: Three endometrial stromal nodules (ESN), 13 endometrial stromal sarcomas (ESS), and 7 undifferentiated endometrial sarcomas (UES) were reviewed. Three metastases from one of the ESS were also analyzed. Nine of these tumors (1 ESN, 8 ESSs, and 1 UES) exhibited unusual histological features, including smooth muscle (3), sex cord (7), epithelioid (1), fibromyxoid (1), and skeletal muscle (2) differentiation. A tissue microarray (TMA) was prepared and FISH analysis was performed using break-apart and fusion probes for JAZF1, SUZ12, EPC1, and PHF1 genes.
Results: FISH was successful in 22 cases and rearrangements involving JAZF1, SUZ12, EPC1, and PHF1 genes were detected in 10 of the 22 (45%) uterine tumors, including 2 of the 3 ESNs, and 8 of 12 ESSs. Genetic rearrangements were found neither in the three metastases of the ESS nor in any of the UES. Noteworthy, a correlation between sex cord differentiation and PHF1 rearrangement was encountered in endometrial stromal sarcomas (p=0.008).
Conclusions: In our series, all ESSs showing sex cords had PHF1 genetic rearrangement, suggesting that such rearrangement may induce sex cord differentiation.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 11:30 AM
Proffered Papers: Section E, Tuesday Morning