HER2 protein overexpression and gene amplification in upper urinary tract transitional cell carcinoma: systematic analysis applying tissue microarray technique.

OBJECTIVES: To investigate HER2 (c-erbB-2) protein overexpression and HER2 gene amplification in upper urinary tract transitional cell carcinoma (TCC) with respect to its association with tumor grade and stage, as well as the prognostic significance.
METHODS: A total of 53 consecutive TCC specimens were analyzed immunohistochemically (HercepTest) and with fluorescence in situ hybridization applying a tissue microarray technique.
RESULTS: Overall, HER2 immunoreactivity (expression) was detected in 28 of 53 TCC specimens and tended to be stronger in high-stage (8 [36%] of 22 pT1 versus 20 [65%] of 31 pT2-T3; P = 0.06) and high-grade (11 [39%] of 28 low-grade versus 17 [68%] of 25 high-grade; P = 0.054) tumors. Weak overexpression (HercepTest score 2+) was seen in 9 cases (17%) and was associated with angioinvasion (P = 0.02) and had independent prognostic significance with respect to metastasis-free survival (risk ratio 9.6; P = 0.03). Low HER2 amplification was present in four TCC specimens (9%), with HER2/chromosome 17 ratios of 2.03, 2.77, 2.91, and 3.39, and polysomy of chromosome 17 was present in another 3 cases (7%). HER2 amplification and/or polysomy of chromosome 17 prevailed in high-stage (0 [0%] of 20 pT1 versus 7 [27%] of 26 pT2-T3; P = 0.01) and high-grade (1 [4%] of 24 low-grade versus 6 [27%] of 22 high-grade; P = 0.04) tumors, but lacked independent prognostic significance. Of nine TCC specimens with weak HER2 overexpression (HercepTest score 2+), 3 (33%) showed low HER2 amplification and two others had polysomy of chromosome 17.
CONCLUSIONS: HER2 overexpression and HER2 gene amplification were infrequent in our series. Thus, only a small number of patients with upper urinary tract TCC might benefit from HER2-targeted (Herceptin) cancer therapy.