Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Pathol Res Pract. 2022 Sep;237:154028. doi: 10.1016/j.prp.2022.154028. Epub 2022 Jul 18.
Uroplakin 1A (Upk1a) protein is relevant for stabilizing and strengthening urothelial cells and helps to prevent them from rupturing during bladder distension. Based on RNA expression data Upk1a is expressed in a limited number of normal tissues and tumors. To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1a immunohistochemistry, a tissue microarray containing 6929 samples from 115 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed. Upk1a positivity was found in 34 (29.6 %) different tumor types including 9 (7.8 %) tumor types with at least one strongly positive case. The highest rates of Upk1a positivity were seen in various subtypes of urothelial neoplasms (42.6-98 %) including Brenner tumors of the ovary (64.9 %) followed by neoplasms of the thyroid (10.4-33.3 %). In urothelial tumors, Upk1a staining predominated at the cell membranes and staining intensity was often moderate to strong. In thyroidal neoplasms the staining was mostly purely cytoplasmic and of low to moderate intensity. Upk1a positivity was also seen in up to 15 % of cases in 25 additional tumor categories but the staining intensity was often cytoplasmic and the intensity was usually judged as weak and only rarely as moderate. Within non-invasive (pTa) tumors, the Upk1a positivity rate decreased from 94 % in pTa G2 (low grade) to 90.1 % in pTa G3 (p = 0.012) and was even lower in muscle-invasive carcinomas (41.5 %; p < 0.0001 vs pTaG3). Within muscle invasive carcinomas, Upk1a expression was unrelated to nodal metastasis (p > 0.05) and patient outcome (p > 0.05). In conclusion, Upk1a immunohistochemistry is a potentially useful and specific diagnostic marker for the distinction of urothelial carcinomas from other neoplasms. However, its sensitivity is less than 50 % in muscle-invasive cancers because Upk1a expression decreases during grade and stage progression.
尿路上皮蛋白 1A（Upk1a）蛋白对于稳定和增强尿路上皮细胞很重要，有助于防止膀胱扩张时细胞破裂。基于 RNA 表达数据，Upk1a 在有限数量的正常组织和肿瘤中表达。为了全面评估 Upk1a 免疫组化的潜在诊断和预后效用，分析了包含 115 种不同肿瘤类型和亚型的 6929 例样本和 76 种不同正常组织类型的 608 例样本的组织微阵列。发现 34 种（29.6%）不同的肿瘤类型存在 Upk1a 阳性，包括 9 种（7.8%）至少有 1 例强阳性病例的肿瘤类型。Upk1a 阳性率最高的是各种尿路上皮肿瘤亚型（42.6-98%），包括卵巢 Brenner 肿瘤（64.9%），其次是甲状腺肿瘤（10.4-33.3%）。在尿路上皮肿瘤中，Upk1a 染色主要位于细胞膜上，染色强度通常为中到强。在甲状腺肿瘤中，染色主要为细胞质，强度为低到中。在另外 25 种肿瘤类型中，Upk1a 阳性率高达 15%，但染色强度通常为细胞质，强度通常为弱，仅偶尔为中。在非浸润性（pTa）肿瘤中，Upk1a 阳性率从 pTa G2（低级别）的 94%下降到 pTa G3（90.1%）（p=0.012），在肌肉浸润性癌中更低（41.5%；p<0.0001 与 pTaG3 相比）。在肌肉浸润性癌中，Upk1a 表达与淋巴结转移无关（p>0.05）和患者预后无关（p>0.05）。总之，Upk1a 免疫组化是区分尿路上皮癌与其他肿瘤的一种潜在有用且特异的诊断标志物。然而，其在肌肉浸润性癌症中的敏感性低于 50%，因为 Upk1a 表达在分级和分期进展过程中降低。
