Immunohistochemistry as a paramount tool in research of normal urothelium, bladder cancer and bladder pain syndrome

Abstract

The urothelium, an epithelium of the urinary bladder, primarily functions as blood-urine permeability barrier. The urothelium has a very slow turn-over under normal conditions but is capable of extremely fast response to injury. During regeneration urothelium either restores normal function or undergoes altered differentiation pathways, the latter being the cause of several bladder diseases. In this review, we describe the structure of the apical plasma membrane that enables barrier function, the role of urothelium specific proteins uroplakins and the machinery for polarized membrane transports in terminally differentiated superficial umbrella cells. We address key markers, such as keratins, cancer stem cell markers, retinoic acid signalling pathway proteins and transient receptor potential channels and purinergic receptors that drive normal and altered differentiation in bladder cancer and bladder pain syndrome. Finally, we discuss uncertainties regarding research, diagnosis and treatment of bladder pain syndrome. Throughout the review, we emphasise the contribution of immunohistochemistry in advancing our understanding of processes in normal and diseased bladder as well as the most promising possibilities for improved bladder cancer and bladder pain syndrome management.

A comprehensive analysis of FBN2 in bladder cancer: A risk factor and the tumour microenvironment influencer

“…UC, the major type of BLCA, is a cancer of the epithelial cells destined to be closely related to keratin. Different molecular subtypes of UC commonly have different keratin levels [ 51 ], and keratin expression profiles have been recognized as diagnostic and prognostic markers for BLCA [ 52 ]. According to recent studies, Keratin 17 (K17) targets tumour suppressors and mediates signals to promote tumour growth [ 53 ].…”

Gene Expression-Based Functional Differences between the Bladder Body and Trigonal Urothelium in Adolescent Female Patients with Micturition Dysfunction

“…The present study found that four of five uroplakins, UPK1A , 1B , 2 , and 3A , were highly expressed in the bladder body urothelium. Immunohistochemical assays have shown that uroplakin expression was reduced in intermediate cells and largely absent in basal cells [ 42 , 43 , 44 ].…”

“…They play roles in normal and pathological processes, including allergic responses, infectious and autoimmune diseases, inflammation, and angiogenesis [ 55 , 56 ]. Most of the main pathologic conditions of the bladder, including cancer, urinary tract infections, and BPS/IC, may significantly affect the expression of urothelial receptors and channels, resulting in micturition dysfunctions [ 42 , 50 ].…”

“…Similarly, single-cell transcriptomes of mouse bladder urothelium identified several BPS/IC-regulating genes differentially expressed among different urothelial cell subpopulations [ 49 ], with incomplete urothelial differentiation characterized by reduced expression of uroplakins and the absence of urothelial plaques in the apical plasma membrane, leading to a “leaky” barrier [ 12 , 13 , 14 ]. Together with changes in the expression of sensory proteins, abnormal uroplakin expression is a unifying hallmark of BPS/IC [ 42 ]. However, the lack of significant differences in keratinocyte differentiation, as shown by primary cultures of urothelial biopsies taken from both IC and normal urothelium, is in disagreement with the theory of global and intrinsically abnormal keratinocyte differentiation in BPS/IC [ 63 ].…”

Nursing Acute Pain in Patients With Bladder Cancer: A Case Study

“…Cancerbladder is a prevalent disease associated with substantial morbidity, mortality, and costs. Environmental or occupational exposure to carcinogens, especially tobacco, is a significant risk factor for bladder cancer (Sanli et al, 2017;Zupančič, 2021). In much of the world, smoking and chemical exposure are major risk factors for bladder cancer (Grayson, 2017).…”