{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUroplakin II (UPK2) is a 15‐kDa protein integral to the composition of urothelial plaques, where it contributes to the permeability barrier and structural integrity of the urothelium. Its highly specific expression for urothelial cells underpins its role as a diagnostic marker for urothelial carcinoma (UC). Although UPK2 alone can be moderately sensitive, its high specificity is enhanced when used in conjunction with other markers such as GATA3 and p40, thereby improving the differential diagnosis of UC from mimickers like prostate or, in rare cases, certain breast carcinomas. This diagnostic utility is supported by studies demonstrating UPK2’s expression in a high percentage of UC cases, including both noninvasive and invasive forms, and its absence in nonurothelial tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its diagnostic applications, UPK2 is functionally significant in maintaining normal urothelial biology. Experimental studies have shown that loss or mutation of UPK2 can lead to congenital urinary tract anomalies, emphasizing its pivotal role in urothelial development and integrity. Moreover, the specificity of the UPK2 promoter has been harnessed in the design of dual-specific vectors targeting bladder cancer, and widespread immunohistochemical analyses have mapped its restricted expression profile to urothelial tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent advances have further refined the use of UPK2 in clinical practice by correlating its immunostaining intensity with the molecular subtypes of muscle-invasive bladder cancer. A scoring system based on the proportion of UPK2-positive cells has demonstrated high sensitivity and specificity in predicting luminal versus basal subtypes, outperforming traditional markers such as GATA3 and CK5/6. Furthermore, while strong diffuse cytoplasmic staining is characteristic of urothelial carcinoma, variations in subcellular staining patterns—such as the coarse, granular appearance observed in apocrine-differentiated breast carcinomas—offer an additional diagnostic nuance to avoid misclassification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Tian, Gunes Guner, Hiroshi Miyamoto, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Uroplakin II (UPII), GATA3, and p40 are Highly Sensitive Markers for the Differential Diagnosis of Invasive Urothelial Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Appl Immunohistochem Mol Morphol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAI.0000000000000143"}], "href": "https://doi.org/10.1097/PAI.0000000000000143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25611245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25611245"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wenping Li, Yu Liang, Michael T Deavers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uroplakin II is a more sensitive immunohistochemical marker than uroplakin III in urothelial carcinoma and its variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Pathol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1309/AJCP1J0JPJBPSUXF"}], "href": "https://doi.org/10.1309/AJCP1J0JPJBPSUXF"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25389341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25389341"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mariah Z Leivo, Paul J Elson, David E Tacha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A combination of p40, GATA-3 and uroplakin II shows utility in the diagnosis and prognosis of muscle-invasive urothelial carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pathol.2016.05.008"}], "href": "https://doi.org/10.1016/j.pathol.2016.05.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27594510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27594510"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Laura L Hoang, David E Tacha, Weimin Qi, et al. 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