부산대학교 도서관

Clear Cell Adenocarcinoma (CCA) of the urinary tract is a rare tumor of the urothelial tract, arising most commonly in the urethra and in female patients. Although characterized as a Mullerian-type tumor of the urinary tract by the World Health Organization (WHO), its pathogenesis has not been fully elucidated.;Herein, we report clinical, pathological, and genomic data of primary CCA of the urinary tract. We identified 35 patients with primary CCA of the urinary tract treated at Memorial Sloan Kettering Cancer Center between 2002 and 2023. All cases were re-reviewed to confirm the diagnosis. We performed immunohistochemical (IHC) staining for PAX-8, HNF-1, p53, ARID1A and GATA3. Whole exome sequencing (WES) and/or targeted panel sequencing using MSK-IMPACT assay was performed in 23 cases. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method from the time of most definitive treatment. Thirty patients (86%) were female. The median age at diagnosis was 63 years. The primary tumor location was in the urethra (n=29, 83%). Eighteen tumors were associated with urethral diverticula; there was no association with endometriosis or other Mullerian remnants detected in any of the cases. All patients had invasive disease. Median DFS and OS were 42 (95%CI 23-not reached) and 65 months (95%CI 53-not reached), respectively (Figure 1). IHC for PAX-8 was positive in 32/35 and HNF-1 was positive in 18/18 cases, including those negative for PAX8. Next-generation sequencing analysis revealed an overall low tumor mutational burden (median 3.2 mutations/megabase, IQR 2.7–5.6). The most common oncogenic alterations were found in ARID1A (n=6), TP53 (n=6) and KRAS (n=4). TERT promoter mutation was found in two patients. The mutational signatures were heterogenous across tumors with enrichment in APOBEC and aging singatures, and an aflatoxin exposure signature in 6 patients. Clear cell adenocarcinoma of the urinary tract most commonly affects females and most often arises in the urethra but can occur in the urinary bladder or rarely in the ureter. It represents a molecularly heterogeneous disease with variable mutational profiles and signatures. The most frequently mutated genes are ARID1A, TP53 and KRAS, but unlike urothelial carcinoma, TERT promoter mutation is rare. Our findings confirm that the molecular profile of primary CCA of the urinary tract is more similar CCA of the female genital tract than to urothelial carcinoma. [ABSTRACT FROM AUTHOR]