ErbB2, ErbB3 and ErbB4 expression in urothelial tumors of the upper urinary tract and their prognostic significance.
OBJECTIVE
ErbB family represents a promising therapeutic target in upper urinary tract urothelial carcinoma (UUTUC). Our study aimed to correlate ErbB2, ErbB3 and ErbB4 expression in UUTUC with other clinicopathological parameters as well as patient outcome.


METHODS
ErbB2, ErbB3 and ErbB4 were immunohistochemically assessed in 99 consecutive UUTUC specimens.


RESULTS
With a median follow-up of 52.5 months (range 1-127) 28 patients (28.3%) died 1-95 months after the first surgical treatment and the mean survival was 18.9-24.2 months. ErbB2, ErbB3 and ErbB4 expression was positive in 64.8, 19.5, and 20.8% of the tumors, respectively. Combined expression of all 3 receptors was found in 7.9% of the tumors, combined expression of 2 receptors in 14.5% and 48.7% expressed at least one ErbB receptor. No ErbB expression was found in 28.9% of the tumors. We found no significant correlation between ErbB2, ErbB3 and ErbB4 expression with tumor stage, grade, recurrence or cancer specific survival apart from the inverse relation between ErbB2 expression and time to recurrence (p=0.027).


CONCLUSIONS
Of the 3 receptors evaluated, neither ErbB3 nor ErbB4 showed any prognostic significance in the UUTUC. ErbB2, however, was inversely associated with recurrence and needs further evaluation in well-designed, prospective, randomized trials.
Urology Department, Athens Naval Hospital, Athens, Greece.
I
I
Galanakis
E
E
Spyropoulos
I
I
Gkialas
A
A
Nomikos
E
E
Souka
D
D
Mitropoulos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D066247:Receptor, ErbB-4; D012189:Retrospective Studies; D015996:Survival Rate; D014571:Urologic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C587689:ERBB4 protein, human