1142P - The Concordance of Her2 Status in Primary and Metastatic Sites of Extramammary Paget's Disease

Abstract

ABSTRACT Background HER2-targeted therapies have been introduced to treat breast and stomach cancers that show HER2 protein overexpression and/or HER2 gene amplification. However, the HER2 status of primary tumors and their corresponding metastatic sites is shown to be heterogeneous in less than 20% of cases. In extramammary Paget's disease (EMPD), HER2 protein overexpression and gene amplification has been shown to occur in 5-80% of cases; however, knowledge regarding the concordance of HER2 status in primary and metastatic sites of EMPD is limited. The aim of this study was to clarify the concordance rate of HER2 status in the primary tumors and metastatic sites of EMPD. Methods Twenty-six tissue blocks of primary tumors and corresponding lymph node metastases were subjected to an immunohistochemistry (IHC) analysis. The IHC scores were classified into four groups (0 to 3+) according to the American Society of Clinical Oncology/College of American Pathologists Guidelines (2007). When the primary tumors and lymph node metastases showed IHC scores of either 2+ or 3 + , the presence of HER2 gene amplification was examined using fluorescence in situ hybridization (FISH) and dual-colored in situ hybridization (DISH). Results mmunohistochemically, 27% (7/26) of the primary tumors and 38% (10/26) of the lymph node metastases showed IHC scores of either 2+ or 3+. When HER2 protein overexpression was classified as being either positive (2 + , 3+) or negative (0, 1+), the concordance rate of the HER2 status of the primary tumors and corresponding lymph node metastases was 85% (22/26). The presence of HER2 gene amplification was examined in six primary tumors and 10 metastatic sites. HER2 gene was amplified in a total of seven cases (27%): four cases in both the primary and metastatic sites, two cases in the metastatic sites only and one case in the primary site only. Conclusion Good concordance of HER2 protein overexpression and gene amplification status was seen in the primary tumors and corresponding lymph node metastases of patients with EMPD. Furthermore, the HER2 gene was found to be always amplified in cases with an IHC score of 3+ and in two cases with an IHC score of 2+ in the lymph node metastases, which is suitable to be targeted for therapy. Disclosure All authors have declared no conflicts of interest.