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Differential Regulation Of Ephb4 And Ephb2 Receptor Tyrosine Kinases In Normal Bladder And Bladder Transitional Cell Carcinoma

March 24, 2017

UroToday - Wesley W Choi, MD and collaborators from the University of Southern California and Northwestern University Feinberg School of Medicine studied EphB4 and EphB2, which are related receptor protein tyrosine kinases that play an important role in organogenesis. EphB4 and EphB2 have been shown to be dysregulated in various epithelial cancers. The objective of this study was to characterize EphB4 and EphB2 expression in normal bladder tissue and in bladder transitional cell carcinoma (TCC).

Matching normal and tumor specimens were prospectively obtained from 41 patients undergoing radical cystectomy for curative intent. EphB4 and EphB2 levels were then assayed with immunofluorescence staining. Normal and TCC bladder cell lines were also studied. EphB4 and EphB2 levels were then correlated with the patient's clinicopathologic characteristics. Histologic examination showed tumor in 35 of the 41 tumor specimens obtained, and normal urothelium in 24 of the 41 normal specimens. Of the 35 tumor specimens obtained, 94% stained positive for EphB4, while none stained positive for EphB2. Of the 24 normal urothelium obtained, none stained positive for EphB4, while 20 of 24 (83%) stained positive for EphB2. All 5 tumor cell lines also showed strong EphB4 signals and no EphB2 signals, while the normal urothelial cell line showed no signal for EphB4 but a strong signal for EphB2. High signal intensity for EphB4 was seen in 27 of 31 cases (87%) of muscle invasive disease. High signal intensity for EphB4 was also seen in 20 of 22 cases (91%) in which carcinoma in situ (CIS) was present.

In conclusion, normal urothelium expresses EphB2 in the vast majority of cases while no expression was observed for EphB4. In contrast, EphB2 was absent in paired bladder TCC tissues, while EphB4 was induced in tumor only. EphB4 signal strength was also correlated with muscle invasive disease and CIS.

From the 2007 annual meeting of the AUA

Reported by UroToday Contributing Editor Christopher P. Evans, MD, FACS

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