4.4 Article

Immunohistochemical and clinicopathological study regarding nardilysin on extramammary Paget's disease

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ARCHIVES OF DERMATOLOGICAL RESEARCH
卷 315, 期 7, 页码 1979-1987

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SPRINGER
DOI: 10.1007/s00403-023-02579-5

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Extramammary Paget's disease; Immunohistochemistry; Nardilysin; p53

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It has been reported that nardilysin (NRDC) is associated with malignancies in a conflicting manner, but its role in cutaneous malignancies has not been investigated. Immunohistochemical staining revealed that NRDC expression is observed in all extramammary Paget's disease (EMPD) cases, while other cutaneous malignancies did not show increased NRDC expression. It was found that NRDC staining was weaker in the marginal parts of EMPD lesions than in the central parts, and tumor cells tended to be distributed beyond the macroscopic skin lesions in these cases, suggesting that decreased NRDC expression in the marginal zones may be associated with the ability of tumor cells to produce the cutaneous manifestation of EMPD.
It has been reported that nardilysin (NRDC), a metalloendopeptidase which regulates various growth factors and cytokines, is associated with malignancies in a conflicting manner, in which it promoted gastric, hepatocellular, and colorectal cancers and suppressed pancreatic ductal adenocarcinoma. However, it has not been investigated how NRDC is associated with cutaneous malignancies for now. Immunohistochemical staining has revealed that NRDC expression is observed in all extramammary Paget's disease (EMPD) cases. Notably, other cutaneous malignancies including basal cell carcinoma, squamous cell carcinoma, and eccrine porocarcinoma, did not show increased NRDC expression in immunohistochemistry. EMPD typically presents several types of lesions including nodules, and positive staining of NRDC on EMPD was observed regardless of the type of lesions. Examination using samples taken from nodular lesions showed that some cases showed heterogenous NRDC expression within each lesion. We also found that NRDC staining was weaker in the marginal parts of EMPD lesion than in the central parts in several cases, and tumor cells tend to be distributed beyond the macroscopic skin lesions in these cases. It was speculated that decreased NRDC expression in the marginal zones of the skin lesions may be associated with the ability of tumor cells to produce the cutaneous manifestation of EMPD. This study suggests that NRDC may be associated with EMPD like other malignancies reported previously.

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