Loss of uroplakin III expression is associated with a poor prognosis in patients with urothelial carcinoma of the upper urinary tract

Ohtsuka, Yukihiro; Kawakami, Satoru; Fujii, Yasuhisa; Koga, Fumitaka; Saito, Kazutaka; Ando, Noboru; Takizawa, Touichiro; Kageyama, Yukio; Kihara, Kazunori

doi:10.1111/j.1464-410x.2006.06158.x

Cited by 23 publications

(10 citation statements)

References 14 publications

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“…Importantly, the loss of UPIII expression was associated with a decrease in cancer-specific survival. Similarly, Ohtsuka et al 17 also found lower UPIII expression in grade III, compared with grades I and II, urothelial tumors, suggesting a correlation between decreased UPIII expression and the level of aggressiveness of the bladder carcinoma. Our study showed that UPIII and UPII protein levels were lower in grade III, compared with grades I and II, bladder tumors ( Table 2).…”

Section: Commentmentioning

confidence: 75%

A Newly Developed Uroplakin II Antibody With Increased Sensitivity in Urothelial Carcinoma of the Bladder

Hoang

Tacha

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Uroplakin II is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. Studies have shown uroplakin II messenger RNA to be expressed in bladder cancer tissues and peripheral blood of patients with urothelial carcinoma. Little is known about the protein expression of uroplakin II in urothelial carcinoma, possibly because of the absence of a commercially available uroplakin II antibody. Pathologists have used the uroplakin III antibody (AU1) to identify tumors of urothelial origin; however, the use of AU1 is limited because of its poor sensitivity.Objectives.-To evaluate a newly developed mouse monoclonal uroplakin II antibody (BC21) in urothelial carcinoma and to compare it with previously developed mouse monoclonal uroplakin III (BC17 and AU1).Design.-Uroplakin II and III antibodies were optimized for staining using a horseradish peroxidase-polymer detection system and were visualized with 3,3 0 -diaminobenzidine.Results.-BC21, BC17, and AU1 demonstrated sensitivities in urothelial carcinoma of the bladder of 79% (44 of 56), 55% (31 of 56) (P ¼ .002), and 34% (19 of 56) (P , .001), respectively. Subsequently, the increased staining sensitivity and intensity of BC21, compared with BC17, was validated in a larger study (134 of 174; 77% and 94 of 174; 54%, respectively) (P , .001). BC21 was found to be highly specific when evaluated in various normal and neoplastic tissues, including prostatic and renal carcinomas.Conclusions. 1 This cancer is particularly associated with high recurrence and progression rates. About 70% of patients with superficial bladder cancer will experience tumor recurrence, and 10% to 15% of that subpopulation will eventually progress to muscle invasion. 2Early diagnosis, when the disease is still at a localized stage, increases the chance of successful treatment. The survival rate for in situ urinary bladder cancer is 97%. Tissue-based biomarkers for early diagnosis of bladder cancer are a major clinical need. Urothelial carcinoma (UC) originates in the urothelium and accounts for more than 90% to 95% of all bladder tumors. Adenocarcinoma and squamous cell carcinoma make up about 1% and 5%, respectively, of bladder carcinomas. Biomarkers expressed in the urothelium, such as uroplakins, could be valuable markers of UC of the bladder. Pathologists have used uroplakin (UP) III (clone AU1) to establish the urothelial origin of the tumor; however, the use of AU1 has been limited because of its poor sensitivity.The asymmetric-unit membrane plaques of the urothelium maintain the blood-urine barrier and prevent cells from rupturing during bladder distention. The molecular constituents of those plaques comprise four transmembrane UP isoforms: UPIa, UPIb, UPII, and UPIII, which are specific differentiation products of the urothelial cells. The UPII is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. 4 The expression of UPII is aberrant in urothelial car...

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Section: Commentmentioning

confidence: 75%

A Newly Developed Uroplakin II Antibody With Increased Sensitivity in Urothelial Carcinoma of the Bladder

Hoang

Tacha

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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“…20 Similar results were found in humans, where loss of UPIII expression was considered a powerful prognostic indicator. 12,16 In a rodent model of chemically induced urinary bladder carcinogenesis, uroplakin expression has been negatively correlated with tumor grade. 15 CK7 labeling was positive and heterogeneous in some cases of urothelial carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Epithelial Urinary Bladder Tumors From Cows With Enzootic Hematuria

Cota¹,

Carvalho²,

Pinto³

et al. 2013

Vet Pathol

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Thirty-nine epithelial bladder tumor samples from 37 animals affected with bovine enzootic hematuria (BEH) were selected for immunohistochemical studies. The expression of structural proteins such as uroplakin III (UPIII) and cytokeratin 7 (CK7) and the cell cycle-related proteins cyclin D1 and p53 were evaluated in urothelial papillomas and carcinomas. Loss of UPIII and CK7 expression was seen in both high-grade and high-stage urothelial carcinomas (P < .001 and P < .02). Cyclin D1 expression showed no statistically significant association with grade or stage. In contrast, p53 immunoreactivity was positive in high-grade and high-stage carcinomas (P < .05 and P < .01), confirming its association with the highest malignant behavior of the bladder tumors in BEH.

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“…8 UPIII shows the highest specificity of this group, but is immunoreactive in only approximately 40-50% of these cases. 9,10 Improved sensitivity can be achieved through a combination of IHC markers, although usefulness in the diagnosis of metastatic lesions and variant morphologies tends to be less robust.…”

Section: Introductionmentioning

confidence: 99%

A combination of p40, GATA-3 and uroplakin II shows utility in the diagnosis and prognosis of muscle-invasive urothelial carcinoma

et al. 2016

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Recently developed antibodies against uroplakin II and ΔNp63 (p40) show utility in diagnosing primary bladder urothelial carcinoma, although application in metastatic bladder cancer and patient outcomes has been less well defined. We evaluated these antibodies by immunostain intensity and H-score, in conjunction with GATA-3 immunoreactivity, in 89 patients with muscle-invasive urothelial carcinoma and 35 paired metastasis. The maintenance of immunoreactivity in metastatic lesions and the association to disease recurrence and survival was assessed. Bladder urothelial carcinoma showed immunoreactivity for GATA-3 in 99% (88/89), p40 in 87% (77/89) and uroplakin II in 80% (71/89) of cases, with a positive correlation between GATA-3 and uroplakin II H-score (0.44; p < 0.0001). All lesions were positive for at least one marker, reinforcing the use of these markers as a panel. In 35 patients with paired lymph node metastasis, uroplakin II and GATA-3 were retained in 90% and 75% of patients, respectively, suggesting these markers may have relatively high sensitivity in diagnosing metastatic urothelial carcinoma. High intensity p40 immunostain (3+), however, was significantly associated with reduced patient survival (p = 0.03). These results suggest that whereas GATA-3 and uroplakin II may be most useful in the diagnosis of urothelial carcinoma metastasis, p40 may be additionally suited as a prognostic marker.

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Loss of uroplakin III expression is associated with a poor prognosis in patients with urothelial carcinoma of the upper urinary tract

Cited by 23 publications

References 14 publications

A Newly Developed Uroplakin II Antibody With Increased Sensitivity in Urothelial Carcinoma of the Bladder

A Newly Developed Uroplakin II Antibody With Increased Sensitivity in Urothelial Carcinoma of the Bladder

Epithelial Urinary Bladder Tumors From Cows With Enzootic Hematuria

A combination of p40, GATA-3 and uroplakin II shows utility in the diagnosis and prognosis of muscle-invasive urothelial carcinoma

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