Her2 Gene Status but Not Protein Expression Stratifies Survival Significantly in Lymph Node Positive Bladder Cancer.
Achim Fleischmann, Diana Rotzer, Roland Seiler, George N Thalmann. University of Bern, Switzerland
Background: Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the most widely used tests to determine Her2 status in cancer. However, there is a controversy about the performance of both tests. Corresponding data in bladder cancer are still limited.
Design: One hundred and fifty lymph node positive patients with urothelial bladder cancer underwent cystectomy and pelvic lymphadenectomy. A tissue microarray was constructed with samples from all primary tumors and matched lymph node metastases. Her2 status was determined on genetic level by FISH and on protein level by IHC using ASCO criteria.
Results: Her2 amplification (15.3%) and borderline amplification (8.8%) are significantly (p=0.003) more frequent in nodal metastases than in primary bladder cancers (8.8% and 5.1%). The same is true for Her2 protein overexpression (score 2+/3+: 25.2% vs. 9.4%, p<0.001). FISH and IHC results are only moderately correlated (kappa in primary tumors: 0.566, in metastases: 0.673) with 38.5% of the amplified primary tumors being immunohistochemically Her2 negative but amplification in all immunohistochemically strongly positive (3+) primary tumors; corresponding data from the metastases are 19% and 91.5%. Patients with Her2 amplification in the metastases have more (median 5 vs. 3, p=0.262) and larger metastases (max. diameter median 1.5 cm vs. 1.0 cm, p=0.263), however, these differences are not significant. Corresponding data based on IHC always have higher p-values. Her2 amplification in the primary tumor significantly predicts poor outcome (p=0.044) but misses to add independent prognostic information (p=0.074). IHC based survival stratification is unsuccessful.
Conclusions: Her2 FISH data are only moderately correlated with IHC results, which do not detect a substantial part of the amplified tumors. Together with successful survival stratification by FISH but not by IHC this suggests an advantage of FISH for patient selection for anti-Her2 therapies.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 171, Tuesday Morning