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Published on: December 5, 2017
Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer
J Tschui1, E Vassella, N Bandi
1Institute of Pathology, University of Bern, Bern, Switzerland.
Abstract:
Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.
Insights
HER2 amplified urothelial bladder cancer (UBC) shows distinct morphology and frequently expresses HER2 protein, indicating potential benefit from HER2-targeted therapies. Genetic analysis revealed specific mutations in some amplified tumors.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Urothelial bladder cancer (UBC) is being investigated for HER2-targeted therapy benefits.
- HER2 amplification in UBC may predict treatment response.
- Limited data exists on the histomorphology, HER2 protein expression, and gene alterations in HER2-amplified UBC.
Purpose of the Study:
- To characterize the histomorphological features of HER2-amplified UBC.
- To assess HER2 protein expression patterns in these tumors.
- To identify HER2 gene alterations in HER2-amplified UBC.
Main Methods:
- Comparative analysis of histopathological features between 13 HER2-amplified and 13 non-amplified UBC cases.
- Immunohistochemistry for HER2 protein expression.
- Screening for HER2 gene mutations in exons 19 and 20.
Main Results:
- HER2-amplified UBC exhibited diverse histological variants, frequent micropapillary components (77%), and significant tumor-associated inflammation.
- Strong HER2 protein positivity was observed in 77% of amplified tumors; 23% were HER2 negative.
- One amplified tumor had a HER2 exon 19 mutation (D769N); others were wild type.
Conclusions:
- HER2-amplified UBC possesses unique morphological characteristics.
- Diffuse HER2 protein expression in these tumors suggests suitability for HER2-targeted therapies.
- HER2 gene mutations may offer additional insights for molecular testing in UBC.
