Radoslav Matěj

TRPS1 expression in 451 tubo-ovarian tumours: a potential prognostic marker for high-grade serous carcinoma.

Trichorhinophalangeal syndrome type 1; transcriptional repressor GATA binding 1 (TRPS1), a member of the GATA transcription factor family, functions primarily as a transcriptional repressor. TRPS1 is frequently utilised as a diagnostic marker for breast carcinoma, although its specificity is lower than previously believed. Moreover, TRPS1 is expressed in various solid tumours originating from the skin, salivary glands, soft tissues, prostate, urothelium, and female genital tract. The current study evaluated the diagnostic and prognostic significance of TRPS1 in 451 primary tubo-ovarian tumours. The cohort included 94 high-grade serous carcinomas (HGSCs), 81 low-grade serous carcinomas (LGSCs), 31 micropapillary serous borderline tumours (mSBTs), 92 clear cell carcinomas (CCCs), 52 endometrioid carcinomas (ECs), 31 mucinous carcinomas (MCs), and 70 mucinous borderline tumours (MBTs). Immunohistochemical analysis was performed using tissue microarrays following standardised protocols. Clinical data were analysed to determine the prognostic relevance of TRPS1 expression. TRPS1 expression was detected in 47% of HGSCs, 44% of ECs, 35% of CCCs, 19% of LGSCs, and 29% of mSBTs with complete negativity in MC/MBT. TRPS1-negative HGSC cases had higher recurrence rates than those with positive staining. Furthermore, TRPS1 expression significantly correlated with improved metastasis-free survival in HGSC cases. These findings suggest that TRPS1 may serve as an independent prognostic marker for HGSC. Despite varying expression rates across primary tubo-ovarian carcinomas, the routine use of TRPS1 in the differential diagnosis seems to be limited, ​as other robust immunohistochemical markers are available for distinguishing the individual subgroups. Further research is needed to clarify the specific functions and clinical implications of TRPS1 in tubo-ovarian cancer.

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of ESS, UTROSCT, and UUS with Prognostic Insights.

Low-grade endometrial stromal sarcomas (LG-ESS), high-grade ESS (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors are distinct non-smooth muscle cell neoplasms with varying clinical outcomes, often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of low-grade and high-grade characteristics are recognized. To address these challenges, we analyzed RNA-seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into 2 partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. uterine tumors resembling ovarian sex cord tumors expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into 2 mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell-differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.

Somatic Genomic and Transcriptomic Characterization of Primary Ovarian Serous Borderline Tumors and Low-Grade Serous Carcinomas

Low-grade serous carcinoma (LGSC) may develop from serous borderline tumor (SBT) tissue, where the micropapillary type (mSBT) presents the highest risk for progression. The sensitivity of LGSC to standard chemotherapy is limited, so alternative therapeutic approaches, including targeted treatment, are needed. However, knowledge about the molecular landscape of LGSC and mSBT is limited. A sample set of 137 pathologically well-defined cases (LGSC, 97; mSBT, 40) was analyzed using capture DNA next-generation sequencing (727 genes) and RNA next-generation sequencing (147 genes) to show the landscape of somatic mutations, gene fusions, expression pattern, and prognostic and predictive relevance. Class 4/5 mutations in the main driver genes (KRAS, BRAF, NRAS, ERBB2, USP9X) were detected in 48% (14/29) of mSBT cases and 63% (47/75) of LGSC cases. The USP9X mutation was detected in only 17% of LGSC cases. RNA next-generation sequencing revealed gene fusions in 6 of 64 LGSC cases (9%) and 2 of 33 mSBT cases (9%), and a heterogeneous expression profile across LGSC and mSBT. No molecular characteristics were associated with greater survival. The somatic genomic and transcriptomic profiles of 35 mSBT and 85 LGSC cases are compared for the first time. Candidate oncogenic gene fusions involving BRAF, FGFR2, or NF1 as a fusion partner were identified. Molecular testing of LGSC may be used in clinical practice to reveal therapeutically significant targets.