Uroplakin 1A (MSVA-735M)

Mouse monoclonal / IgG 1:100-1:200 Research Use Only Cell surface Human MSVA-735M UP1A; UPIA; UPKA; TSPAN21 Urinary bladder:A strong membranous and cytoplasmic Upk1a immunostaining should be seen in the urothelium (the staining can be limited to the top 1/3 or 2/3 of the urothelium). Colon:Upk1a immunostaining should be absent in all cells of the colon mucosa. Uroplakin 1A is marker for urothelium and urothelial tumors. The Uroplakin 1A (Upk1a) protein is coded by the UPK1b gene located at 19q13.12 . Upk1a is one out of 5 known uroplakin (Upk) protein particles that cooperatively form apical asymmetric unit membrane (AUM) plaques which play an important role in the stabilization and  strengthening of epithelial cells that line the bladder. These AUM plaques enable the inner bladder membrane to stretch and prevent urothelial cells from rupturing during bladder distension. Upks are assembled in the endoplasmic reticulum (ER), where they heterodimerize prior to escaping the ER. Upk1a heterodimerizes with Upk2 and Upk1b heterodimerizes with Upk3. Upk heterodimers subsequently form heterotetramers which then combine as concentric hexameric rings that are packaged into vesicles and trafficked to the cell surface. AUMs and Upk proteins may have a role in mediating membrane permeability and signal transduction events that are involved in the regulation of cell development, activation, growth, and motility. Uroplakin 1A staining pattern in Normal Tissues with antibody MSVA-735M (images are shown in our “Normal Tissue Gallery”) Brain Cerebrum Negative. Cerebellum Negative. Endocrine Tissues Thyroid Negative. Parathyroid Negative. Adrenal gland Negative. Pituitary gland Negative. Respiratory system Respiratory epithelium Negative. Lung Negative. Gastrointestinal Tract Salivary glands Negative. Esophagus A faint/weak/moderate Upk1a staining can occur in some cell layers (middle third) of the squamous epithelium. Stomach Negative. Duodenum Negative. Small intestine Negative. Appendix Negative. Colon Negative. Rectum Negative. Liver Negative. Gallbladder Negative. Pancreas Negative. Genitourinary Kidney Negative. Urothelium Upk1a immunostaining is strongest in the urothelium. Here the staining is particularly strong in the top third cell layers including umbrella cells. Staining is less intense or even absent in basal cell layers. Male genital Prostate A focal weak to moderate UpK1a staining c... A positive Upk1a immunostaining is most commonly seen in urothelial carcinomas. It can also occur in squamous cell  carcinomas and – rarely – in other cancers. The TCGA findings on Uroplakin 1A RNA expression in different tumor categories have been summarized in the Human Protein Atlas. Urinary bladder- Muscle-invasive urothelial carcinoma with strong Upk1a immunostaining of tumor cells Kidney, pelvis- Invasive urothelial carcinoma with strong, predominantly membranous Upk1a immunostaining of tumor cells Thyroid- Follicular cancer with moderate to strong, predominantly cytoplasmic Upk1a staining of tumor cells Cancer tissue gallery Uroplakin 1a (MSVA-735M) publication summary Relevant publication: Reiswich et al. Large-scale human tissue analysis identifies Uroplakin 1a as a putative diagnostic marker for urothelial cancer. Published in Pathology Research and Practice 2022 Jul 18;237:154028. Epub ahead of print. PMID: 35872365. A total of 5’323 tumors were successfully analyzed from 115 different tumor categories by using the following protocol: Heat-induced antigen retrieval for 5 minutes in an autoclave at 121°C in pH7,8 Target Retrieval Solution buffer. MSVA-735M at a dilution of 1:150 at 37°C for 60 minutes. Visualization of bound antibody by the EnVision Kit (Dako, Agilent). This protocol was also used for all stainings depicted in our tumor and normal tissue galleries. The study results showed a striking predominance of Upk1a expression in urothelial neoplasms (42.6–98%) including Brenner tumors of the ovary (64.9%), followed by neoplasms of the thyroid gland (31.8–33.3%). The authors also observed Upk1a po... IHC users have different preferences on how the stains should look like. Some prefer high staining intensity of the target stain and even accept some background. Others favor absolute specificity and lighter target stains. Factors that invariably lead to more intense staining include higher concentration of the antibody and visualization tools, longer incubation time, higher temperature during incubation, higher temperature and longer duration of the heat induced epitope retrieval (slide pretreatment). The impact of the pH during slide pretreatment has variable effects and depends on the antibody and the target protein. All images and data shown here and in our image galleries are obtained by the manual protocol described below. Other protocols resulting in equivalent staining are described as well. Manual protocol Freshly cut sections should be used (less than 10 days between cutting and staining). Heat-induced antigen retrieval for 5 minutes in an autoclave at 121°C in pH 9 Target Re... The prevalence and clinical significance of Upk1a expression in cancer is unknown. There are two ways how the specificity of antibodies can be documented for immunohistochemistry on formalin fixed tissues. These are: 1. Comparison with a second independent method for target expression measurement across a large number of different tissue types (orthogonal strategy), and 2. Comparison with one or several independent antibodies for the same target and showing that all positive staining results are also seen with other antibodies for the same target (independent antibody strategy). Orthogonal validation: For the antibody MSVA-735M specificity is suggested by the strong concordance of the immunostaining data with data from three independent RNA screening studies, including the Human Protein Atlas (HPA) RNA-seq tissue dataset, the FANTOM5 project, and the Genotype-Tissue Expression (GTEx) project, which are all summarized in the Human Protein Atlas (Tissue expression Uroplakin 1A) . RNA expression was almost exclusively detected in organs covered by squamous epithelium (e...