JAZF1 and JJAZ1 Gene Fusion in Primary Extrauterine Endometrial Stromal Sarcoma
C Amador-Ortiz, A Roma, XZ Zhu, N Becker, A Chiesa, JD Pfeifer. Washington University, St Louis, MO; Cleveland Clinic, Cleveland, OH
Background: Endometrial stromal sarcoma (ESS) predominantly occurs as a primary tumor of the uterus. The most common cytogenetic abnormality in ESS is t(7;17)(p15;q21), which occurs in 37-80% of cases and results in a JAZF1-JJAZ1 gene fusion. Rare cases of primary extrauterine ESS have been reported, but it remains uncertain whether the genetic features of uterine ESS are also characteristic of extrauterine ESS. The present study evaluates the prevalence of the t(7;17) and JAZF1-JJAZ1 gene fusion in a series of primary extrauterine ESS by both reverse transcriptase polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH).
Design: Cases of primary extrauterine ESS were identified from departmental files. Conventional nested RT-PCR was performed on RNA extracted from paraffin embedded tumor tissue using primers complementary to sense and antisense JAZF1 and JJAZ1 sequences; RNA integrity was confirmed by RT-PCR for GAPDH. Interphase FISH was performed to detect t(7;17)(p15;q21) using a break-apart strategy for both JAZF1 and JJAZ1; for each case, 200 nuclei were analyzed. Cases of uterine ESS with known translocation status served as positive and negative controls for RT-PCR and FISH.
Results: The series of extrauterine ESS included three cases arising in the ovary and three arising in the abdominopelvic cavity unassociated with the gynecologic tract. All cases had morphologic features of conventional low grade ESS; a focal sex cord-like pattern was present in one case. None of the cases had evidence of intrauterine pathology. JAZF1-JJAZ1 fusion transcripts were not detected by RT-PCR in any of the cases of extrauterine ESS, although all contained amplifiable RNA. None of the cases showed evidence of a rearrangement involving either JAZF1 or JJAZ1 by interphase FISH. Expected results of RT-PCR and FISH assays were observed in all controls.
Conclusions: Our findings demonstrate that the t(7;17)(p15;q21) and associated JAZF1-JJAZ1 fusion transcripts are not universally present in primary extrauterine ESS. When our results are pooled with published case reports of primary extrauterine ESS, the t(7;17) and/or JAZF1-JJAZ1 are present in 25% of cases, a prevalence somewhat below that reported for uterine ESS. While molecular testing for the t(7;17) and associated gene fusion may be useful for confirming primary extrauterine ESS, the low prevalence of the genetic aberration limits the clinical utility of the testing.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 146, Monday Morning