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HER2 oncogene amplification in extramammary Paget's disease
M Tanskanen1, T Jahkola, S Asko-Seljavaara
1Department of Pathology, Helsinki University and Helsinki University Central Hospital, Finland. maarit.tanskanen@helsinki.fi
Histopathology
|June 6, 2003
Summary
HER2 gene amplification and protein over-expression are common in extramammary Paget's disease (EMP), suggesting potential for HER2-targeted therapies in patients with HER2-positive EMP.
Area of Science:
- Oncology
- Molecular Biology
- Dermatopathology
Background:
- Extramammary Paget's disease (EMP) is a rare intra-epidermal adenocarcinoma.
- Previous reports suggest HER2 oncoprotein over-expression in EMP.
Purpose of the Study:
- To investigate HER2 (human epidermal growth factor receptor 2) gene amplification and protein over-expression in EMP skin samples.
- To determine the relationship between HER2 amplification and over-expression in EMP.
Main Methods:
- Chromogenic in-situ hybridization (CISH) to detect HER2 gene amplification.
- Immunohistochemistry (IHC) to assess HER2 protein expression levels (3+ intensity).
- Analysis of 23 EMP patient samples and 10 mammary Paget's disease control samples.
Main Results:
- HER2 gene amplification was detected in 43% (10/23) of EMP lesions.
- HER2 protein over-expression (3+ IHC) was observed in 52% (12/23) of EMP tumors, including all cases with gene amplification.
- Mammary Paget's disease controls showed universal HER2 amplification and over-expression.
Conclusions:
- HER2 protein over-expression in EMP is frequent and directly caused by gene amplification.
- These findings support the potential utility of HER2-targeted immunotherapies for patients with HER2-positive EMP.