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Multicenter Study
. 2010 Apr;21(4):815-819.
doi: 10.1093/annonc/mdp488. Epub 2009 Nov 4.

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

M Laé  1 , J Couturier  2 , S Oudard  3 , F Radvanyi  4 , P Beuzeboc  5 , A Vieillefond  6
Affiliations
Multicenter Study

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

M Laé et al. Ann Oncol. 2010 Apr.

Abstract

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.

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Figures

Figure 1.
Figure 1.
Pathologic immunohistochemistry labeling results of invasive urothelial bladder carcinoma. (A) Detrusor-invading urothelial bladder carcinoma (hematoxylin–eosin ×40 magnification); (B) HER2 2+ membranous expression (×40 magnification); (C) HER2 3+ membranous expression (×40 magnification); and (D) patterns of heterogeneous 3+ and 2+ HER2 membranous expression within the same tumor (×20 magnification).
Figure 2.
Figure 2.
Interphase FISH on paraffin-embedded tumor tissue section results. (A) Nonamplified tumor cells: two green fluorescein isothiocyanate-labeled (centromere 17) and two red rhodamine-labeled signals (HER2 gene) present in each nucleus and (B) tumor cells with HER2 gene amplification: clusters of HER2 gene signals associated with two copies of centromere 17 present in each nucleus.
See this image and copyright information in PMC

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