Annals of Oncology Advance Access published online on November 4, 2009
Annals of Oncology, doi:10.1093/annonc/mdp488
Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients
1 Departments of Pathology
2 Departments of Genetics, Institut Curie
3 Department of Medical Oncology, Hôpital Européen Georges Pompidou
4 Medical Recherche Unit 144-Oncologie Moléculaire-Centre national de la recherche scientifique, Institut Curie
5 Department of Medical Oncology, Institut Curie
6 Department of Pathology, Hôpital Cochin, Paris, France
* Correspondence to: Dr M. Laé, Department of Pathology, Institut Curie, 26 rue d'Ulm, 75231 Paris cedex 05, France. Tel: +33-1-44-32-42-54; Fax: +33-1-44-32-40-72; E-mail: marick.lae{at}curie.net
Background: This study assessed the human epidermal growth factor receptor-2 (HER2) protein expression and its relationship with gene amplification in invasive bladder carcinoma, using the same criteria than for breast cancer.
Patients and methods: In 1005 patients, paraffin-embedded tissues of transurethral resection or cystectomy were evaluated by immunohistochemistry (IHC), using antibodies against HER2. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH.
Results: HER2 overexpression was observed in 93 (9.2%) tumors (2+: 42 tumors and 3+: 51 tumors). Using FISH, all HER2 3+ tumors had a gene amplification, whereas no amplification was found in 2+ tumors. Intratumoral heterogeneity was observed in 35% of cases. These tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH.
Conclusions: This study showed that 5.1% of invasive bladder carcinomas had a HER2 gene amplification. These findings may have clinical implications for the management of patients with HER2-positive locally advanced or metastatic bladder cancer, as they could be potential candidates for targeted therapy.
FISH, HER2, immunohistochemistry, targeted therapy, urothelial bladder carcinoma
Received for publication June 14, 2009. Revision received August 6, 2009. Accepted for publication September 17, 2009.