TY - JOUR
T1 - Clinicopathologic Characterization of GREB1 -rearranged Uterine Sarcomas With Variable Sex-Cord Differentiation
AU - Lee, Cheng Han
AU - Kao, Yu-Chien
AU - Lee, Wan Ru
AU - Hsiao, Yi Wen
AU - Lu, Tzu Pin
AU - Chu, Chia Ying
AU - Lin, Yi Jia
AU - Huang, Hsuan Ying
AU - Hsieh, Tsung Han
AU - Liu, Yun Ru
AU - Liang, Cher Wei
AU - Chen, Tom Wei Wu
AU - Yip, Stephen
AU - Lum, Amy
AU - Kuo, Kuan Ting
AU - Jeng, Yung Ming
AU - Yu, Shih Chen
AU - Chung, Yung Chuan
AU - Lee, Jen Chieh
N1 - Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5′-ESR1/GREB1 and 3′-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, -inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.
AB - Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5′-ESR1/GREB1 and 3′-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, -inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.
KW - ESR1
KW - GREB1
KW - sex cord tumor
KW - uterine sarcoma
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UR - http://www.scopus.com/inward/citedby.url?scp=85067895984&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001265
DO - 10.1097/PAS.0000000000001265
M3 - Article
C2 - 31094921
AN - SCOPUS:85067895984
SN - 0147-5185
VL - 43
SP - 928
EP - 942
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 7
ER -