Immunohistochemical Study of HER2 and TUBB3 Proteins in Extramammary Paget Disease

Metastatic extramammary Paget disease (EMPD) is a potentially fatal malignancy for which effective chemotherapy and good biomarkers are desirable for management. We investigated the status of human epidermal growth factor receptor (HER2) and neuronal beta-tubulin isotype (class III beta-tubulin; TUBB3), whose overexpression is a factor involved in resistance of tumor cells to taxane derivatives) in 32 patients with EMPD. HER2 status was evaluated by immunohistochemistry followed by fluorescence in situ hybridization, and TUBB3 status was evaluated by immunohistochemistry. On the basis of the US Food and Drug Administration-approved criteria, 20 (63%) of the 32 EMPD tumors were found to overexpress HER2. Positive immunoreactivity for TUBB3 was observed in 7 (22%) of the 32 patients. Although some clinicopathologic variables (nodule formation, depth of tumor cells, presence of lymph node metastasis, and serum carcinoembryonic antigen level) were significantly associated with disease outcome (P < 0.05), HER2 gain or aberrant TUBB3 expression showed no significant correlation.. However, the higher incidence of HER2 gain and the relatively lower incidence of aberrant TUBB3 expression suggested that HER2-targeted immunotherapy combined with taxane derivatives is warranted for metastatic EMPD, and that HER2 and TUBB3 status might be a good biomarker for determining the most appropriate therapeutic modality.