Correlation of Immunohistochemistry for HER2 with Bright Field Dual ISH (DDISH) in Extramammary Paget Disease
Donelle Cummings, Raymond R Tubbs, J Jordi Rowe, Chris Lanigan, Steven D Billings. Cleveland Clinic, Cleveland, OH
Background: Immunohistochemistry (IHC) for HER2 expression is frequently positive in extramammary Paget disease (EMP). Like HER2 positive breast cancer, treatment of EMP with trastuzumab, a monoclonal antibody directed against HER2, has shown antitumoral activity. In the setting of breast cancer, evidence of gene amplification is often required before initiating HER2-targeted therapy. Unlike in breast carcinoma, little work has been done correlating immunohistochemistry for HER2 and HER2 gene amplification in EMP. We compared IHC with a bright field in situ hybridization assay for determination of HER2 status in EMP.
Design: Cases coded as EMP were retrieved and immunostained for HER2 (4B5) and also evaluated by dual color dual hapten bright field silver in situ hybridization (DDISH), and correlated with IHC expression (Pathway HER2; 4B5 rabbit monoclonal antibody; Ventana Medical Systems) with cell line expression controls. Demographics were also reviewed.
Results: Nine cases were evaluated. 7/9 were women and 6/9 were from the vulva and 3/9 were perianal. 7/9 showed staining by IHC for HER2. Of these cases, 5/7 were 1+, 1/7 was 2+, 1/7 was 3+. HER2 gene amplification detected by DDISH with protein over-expression, was seen in three cases (one 3+ IHC, one 2+ IHC, and one 1+ IHC), the latter two demonstrating low level, but definitive HER2 gene amplification.
Conclusions: IHC for HER2 expression in EMP may be a useful adjunctive diagnostic tool. HER2 gene amplification as assessed by DDISH was inconsistently associated with overt HER2 protein over-expression by IHC. Low level gene amplification may occur in a greater proportion of EMP patients as compared with breast carcinoma, but a larger cohort of patients will be required to fully evaluate this pattern. In the setting of EMP, DDISH may be more sensitive than IHC for detecting patients eligible for trastuzumab based therapy, which could have potential therapeutic implications for patients with unresectable or advanced EMP. Additional cases of EMP need to be evaluated by simultaneous IHC and DDISH.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 107, Tuesday Morning