| Autor: |
Flídrová, Miroslava, Hájková, Nikola, Hojný, Jan, Dvořák, Jiří, Michálková, Romana, Krkavcová, Eva, Laco, Jan, McCluggage, W. Glenn, Giordano, Giovanna, Silini, Enrico Maria, Michalová, Květoslava, Bizoń, Magdalena, Němejcová, Kristýna, Dundr, Pavel, Bártů, Michaela Kendall |
| Zdroj: |
Modern Pathology; 20240101, Issue: Preprints |
| Abstrakt: |
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign manner, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving NCOA1-3. We performed a comprehensive clinicopathological, morphologic, immunohistochemical, and molecular analysis on a cohort of 35 UTROSCT. The tumors exhibited various architectural patterns (diffuse, corded/trabecular, tubular, sertoliform, fascicular, whorled, nested, microfollicular, and pseudoglandular), often in combination. The immunohistochemical analysis confirmed the polyphenotypic immunoprofile, often with coexpression of sex cord–stromal, smooth muscle, and epithelial markers, as well as hormone receptors. Next-generation sequencing RNA analysis revealed recurrent NCOA1-3gene fusions in 22/32 analyzed cases (69%), including ESR1::NCOA3(11/22), GREB1::NCOA2(7/22), ESR1::NCOA2(3/22), and GREB1::NCOA1(1/22). Tumor mutation burden was low in all cases. The fusion-positive cases exhibited statistically significant association with whorled architecture, conversely necrosis was associated with fusion-negative status. We did not find a significant relationship between any architectural pattern and GREB1alterations, but the NCOA2-altered tumors were associated with pseudoglandular architecture. The GREB1-altered cases occurred in older patients and tended to be more often intramural masses compared with ESR1-altered cases. On the contrary, the ESR1-altered cases presented more often like submucosal or polypoid tumors. Two tumors exhibited aggressive behavior with recurrent disease. Both of these cases harbored a GREB1::NCOA2fusion. Unsupervised hierarchical cluster analysis of our cohort revealed 2 main clusters. The tumors with GREB1or NCOA2fusion cluster together, suggesting that there are underlying molecular differences between these cases and cases with ESR1::NCOA3fusion or without fusion. Our findings contribute to the growing knowledge about a rare neoplasm with currently uncertain biological behavior. |
| Databáze: |
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