Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT)

Abstract

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.

Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior

“…6,8 The mean tumor size was 5.4 cm, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] which is quite similar to the 2 largest series (6.1 cm and 5.1 cm, respectively). As the largest cohort to date, the age of 7 GREB1::NCOA2 patients in our study was younger than 5 previously reported patients 7,8,11,13,40 (33 y-56 y, mean 48 y vs. 51 y-74 y, mean 60 y, P = 0.049). Five GREB1::NCOA1 patients were significantly younger than the 6 reported cases (50 y vs. 68 y, P = 0.001).…”

“…6 Recurrent NCOA1-3 rearrangements in UTROSCT have been described in recent reports, with GREB1 and ESR1 as the 2 most frequent partner genes. [7][8][9] GREB1:: NCOA1, GREB1::NCOA2, ESR1::NCOA2, and ESR1:: NCOA3 fusions have all been reported in UTROSCT. In addition, CTNNB1 fused with GREB1 was reported in 1 UTROSCT.…”

Spindle Cell Sarcoma of the Uterus Harboring MEIS1::NCOA1 Fusion Gene and Mimicking Endometrial Stromal Sarcoma

“…[23][24][25] Alternatively, NCOA1 (nuclear receptor coactivator 1) and NCOA2 (nuclear receptor coactivator 2) genes are located on chromosomes 2p23.3 and 8q13.3, respectively, and encode for proteins that act as a coactivator for nuclear hormone receptors including steroid, thyroid, retinoid, and vitamin D. 26 In mesenchymal neoplasms, NCOA1/2 genes are involved in mesenchymal chondrosarcoma (HEY1::NCOA2), 27 a subset of biphenotypic sinonasal sarcoma (PAX3::NCOA1/ 2), 28,29 soft tissue angiofibroma (AHRR::NCOA2), 30 congenital/infantile spindle cell rhabdomyosarcoma (VGLL2::NCOA2, SRF::NCOA2, TEAD1::NCOA2), 31 and uterine tumor resembling ovarian sex cord tumor (ESR1::NCOA2/3, GREB1::NCOA1/2). 32 Nonetheless, the biologic relationship of the contributing gene partners in MEIS1::NCOA1/2 fusion genes is not well explored.…”

Clinicopathological characteristics and genetic variations of uterine tumours resembling ovarian sex cord tumours

“…The adjuvant treatment approaches for these eight patients with recurrence were different, and eventually, three patients died of this tumour. It has recently been found that UTROSCT has the recurrent fusion of NCOA2 or NCOA3, its partner genes are ESR1 and GREB1 14 and recurrence has been associated with GREB1, 5 which underscores the possible value of molecular detection in predicting prognosis. Therefore, for…”

“…FISH was performed as described previously. 5 Briefly, the unstained slides were deparaffinised, pretreated and hybridised to denatured probes. Then, after more than 6 hours of incubation at 37°C, the slides were washed and counterstained with diamidine phenyl indole (DAPI), mounted and analysed using a Zeiss fluorescence microscope (Olympus BX51, Tokyo, Japan).…”