Association of Low Expression of Notch-1 and Jagged-1 in Human Papillary Bladder Cancer and Shorter Survival

Purpose

We investigated the expression of Notch receptors and ligands in normal bladder transitional epithelium and transitional cell carcinoma of the bladder. We also explored its clinical and pathological implications.

Materials and Methods

The expression of Notch-1 to 3, Jagged-1 and Delta-like-1 was detected respectively in 70 cases of bladder carcinoma, 10 of normal urothelium and the 2 cell lines T24 and BIU-87 using immunohistochemistry. Reverse transcriptase-polymerase chain reaction and Western blot were used to assay the expression level of Notch-1 and Jagged-1. The predictive value of this expression for prognosis was investigated by Kaplan-Meier curves and Cox proportional hazards analysis in a multivariate model.

Results

All 5 kinds of Notch factors were intensively stained in normal bladder transitional epithelium immunohistochemically but expression was significantly decreased in tumor tissues. Moreover, expression of the 5 genes in papillary tumors was lower than in invasive tumors but only Notch-1 and Jagged-1 showed a statistically significant difference. Postoperative disease-free survival time in patients with low Notch-1 plus Jagged-1 expression was significantly shorter than that in patients with other expression patterns in papillary tumors (p = 0.014). Multivariate Cox proportional hazards model analysis identified Jagged-1 expression as an independent prognostic factor for disease-free survival (RR 3.09, p = 0.011).

Conclusions

The Notch family expression pattern in papillary bladder transitional cell carcinoma is different from that in invasive bladder transitional cell carcinoma. Low expression of Notch-1 as well as Jagged-1 is potentially a useful marker for survival in patients with papillary bladder transitional cell carcinoma.

Key Words: urinary bladder, carcinoma, transitional cell, signal transduction, receptors, Notch, mortality

Abbreviations and Acronyms: GAPDH, glyceraldehyde-3-phosphate dehydrogenase, PCR, polymerase chain reaction, RT, reverse transcriptase, SHH, sonic hedgehog homolog, TCCB, bladder transitional cell carcinoma