Abstract
Invasive extramammary Paget's disease (EMPD) is relatively rare and is reported to be highly metastatic to lymph nodes or even other organs, including bone. Histologically, EMPD shows significant numbers of lymphocytes around the tumor mass, suggesting the possible development of novel immunomodulatory therapy for EMPD by targeting these infiltrating lymphocytes. Previously, bisphosphonates (BPs) were administered for the treatment of malignancy, especially osteolytic bone disease. Recent reports also suggested that BPs might have a direct antitumor effect through several pathways beyond their beneficial effect on bone metastasis. Among them, the abrogation of immunosuppressive cells, myeloid derived suppressor cells (MDSC), by BPs might be one of the optimal methods to induce an antitumor immune response both locally and at sites remote from the tumor. In this study, we employed immunohistochemical staining for immunosuppressive macrophages and cytotoxic T cells in the lesional skin of patients with noninvasive EMPD and those with invasive EMPD.
Highlights
Extramammary Paget’s disease (EMPD) is a skin adenocarcinoma that generally occurs in the anogenital region [1]
One of the possible explanations for the additional antitumor effects of BPs is that pharmacological inhibition of MMP9 by aminobisphosphonate decreases pro-MMP9 and VEGF in the serum and abrogates the suppressive function of immunosuppressive cells and induces the antitumor immune response both locally and at sites remote from the tumor [6]
The numbers of granulysin+ cells and perforin+ cells were significantly lower in invasive EMPD than in noninvasive EMPD (P < 0.05)
Summary
Extramammary Paget’s disease (EMPD) is a skin adenocarcinoma that generally occurs in the anogenital region [1]. It usually affects older patients, and the lesions commonly develop in the vulva, penis, scrotum, perineum, perianal area, umbilicus, and axilla [1]. Invasive EMPD, relatively rare, is reported to be highly metastatic to lymph nodes (47.1%) or even other organs (17.6%), including bone (5.9%) [2]. Both noninvasive EMPD and invasive EMPD show significant numbers of lymphocytes around the tumor mass. One of the possible explanations for the additional antitumor effects of BPs is that pharmacological inhibition of MMP9 by aminobisphosphonate decreases pro-MMP9 and VEGF in the serum and abrogates the suppressive function of immunosuppressive cells and induces the antitumor immune response both locally and at sites remote from the tumor [6]
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