HER2 Status and Association with Clinical Features and Outcome in Micropapillary Urothelial Carcinoma
William R Sukov, Steven A Schneider, Robert F Tarrell, John C Cheville. Mayo Clinic, Rochester, MN
Background: Given the success of HER2 targeted therapies therapy in breast carcinoma, recent efforts have been made to identify HER2 abnormalities in other malignancies. Recent studies have suggested that HER2 over expression and/or HER2 amplification may be frequent in micropapillary urothelial carcinoma.
Design: Patients with micropapillary urothelial carcinoma treated by cystectomy were identified retrospectively. Clinical and pathologic features were reviewed. Formalin fixed, paraffin embedded tumor tissue was tested for HER2 expression by immunohistochemistry (Ventana) and HER2 status by fluorescence in situ hybridization (Hercept, Abbott Molecular). HER2 score and HER2 status were determined based on CAP/ASCO guidelines for breast carcinoma.
Results: 61 patients with micropapillary urothelial carcinoma were identified. Median follow-up was 9.6 years (4.0-21.1 years) with 36 patients dying from disease. By immunohistochemistry 9 (15%) tumors were HER2=0, 21 (34%) were HER2=1+, 15 (25%) were HER2=2+, and 16 (26%) were HER2=3+. HER2 amplification was identified in 9 (15%) tumors, of which 7 were 3+, 1 was 2+ and 1 was 0 by immunohistochemistry. Corresponding lymph node metastases were tested in 14 cases. HER2 status was concordant in 13 tumors. The 4 HER2 amplified primary tumors showed amplification in metastases. In one case the primary tumor was not amplified and the metastasis showed HER2 amplification. HER2 status was not associated with gender, age or pathologic tumor stage at surgery. Patients with HER2 amplified tumors had shorter cancer-specific survival vs. patients with non-amplified tumors (51% and 13% vs. 86% and 55% 1 and 3 year survival, p<0.001). Cancer-specific survival relative to absolute HER2 number and HER2/CEP17 ratio showed that average HER2 copies >5.7 or a ratio of >1.12 were associated with worse cancer-specific survival (p<0.001, p=0.003 respectively).
Conclusions: HER2 overexpression and HER2 amplification are frequent in micropapillary urothelial carcinoma and HER2 amplification appears to be associated with worse cancer-specific survival. Micropapillary urothelial carcinoma typically demonstrates an aggressive clinical behavior and identification of HER2 abnormalities may provide an important therapeutic option in these patients.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 97, Tuesday Morning