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

Abstract

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. A total of 53 consecutive TCC specimens were analyzed immunohistochemically (HercepTest) and with fluorescence in situ hybridization applying a tissue microarray technique. 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. 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.