Expression of Claudins and Their Prognostic Significance in Noninvasive Urothelial Neoplasms of the Human Urinary Bladder

Abstract

The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.

Overexpression of Claudin-1 is Associated with Advanced Clinical Stage and Invasive Pathologic Characteristics of Oral Squamous Cell Carcinoma

“…A number of studies reported the overexpression of claudin-4 in a variety of cancers [12,14,[17][18][19][20][21][22][23]. The claudin-4 up-regulation was shown to stimulate MMP-2 activity in ovarian carcinoma cells and promote cancer invasion [36].…”

“…The claudin-4 expression was up-regulated in several cancers, including esophageal, gastric, colorectal, pancreatic, ovarian, urothelial, breast, endometrial and prostate cancers [12,14,[17][18][19][20][21][22][23]. Its role in the invasiveness and survival of ovarian cancer cells has also been suggested in an in vitro study [24].…”

A clinical and molecular review of inverted papilloma of the urinary tract: how to handle?

“…A connection between tight junctions in the maintenance of integrity of urothelium and prevention of recurrence of UCC was recognized in 1996 . Szekely et al executed an immunohistochemical study of the expression of claudin 1, 2, 4 and 7 in 15 IPs, 20 urothelial papillomas, 20 PUNLMPs and 20 low grade UCCs . Semi‐quantitative scores of staining intensity multiplied with predefined area‐positivity were calculated for each reaction and revealed that the claudin‐1 expression in urothelial papillomas, PUNLMP and low‐grade UCC was significantly reduced compared to IP.…”

Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

“…Claudin 1,4 and 7 are important members of this Claudin protein family and their expressions show alterations in many different malignancies such as oesophageal, gastric, biliary (Usami et al, 2006;Agarwal et al, 2009;Kwon et al, 2011), ovarian (Kwon et al, 2010), endometrial (Pan et al, 2007;Knoecny et al, 2008), bladder (Boireau et al, 2007;Szekely et al, 2011) renal (Lechpammer et al, 2008), prostate (Landers et al, 2008), breast (Kominsky et al, 2003), cholangiocarcinoma (Bunthot et al, 2012) and pancreatic cancer.…”