Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients.
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.


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.
Laé
M
M
Department of Pathology. Electronic address: marick.lae@curie.net.
Couturier
J
J
Department of Genetics, Institut Curie.
Oudard
S
S
Department of Medical Oncology, Hôpital Européen Georges Pompidou.
Radvanyi
F
F
Medical Recherche Unit 144-Oncologie Moléculaire-Centre national de la recherche scientifique, Institut Curie.
Beuzeboc
P
P
Department of Medical Oncology, Institut Curie.
Vieillefond
A
A
Department of Pathology, Hôpital Cochin, Paris, France.
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D016503:Drug Delivery Systems / Q000379:methods*; D005784:Gene Amplification / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000473:pathology
D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases