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Notes: Abstract:  Claudins are a family of transmembrane proteins involved in cell-to-cell adhesion and are believed to be the main component of tight junctions. Recent studies have suggested that some metastatic solid tumors lack claudin expression. It is unknown whether claudins play a role in cutaneous melanoma. Immunohistochemical studies were performed on tissue microarrays containing 19 benign melanocytic nevi (BN), 21 dysplastic nevi (DN), 23 primary malignant melanomas (MMs), and 31 metastatic melanomas (MMMs) using a polyclonal anti-claudin-1 antibody. Immunoreactivity in tumor cells and associated vessels was graded by intensity and by percentage of reactive cells. Normal epidermis served as internal control (3+ labeling). Cases with at least 2+ labeling in more than 25% of the cells were considered positive. Claudin-1 expression was present in 37% of BN, 24% of DN, 26% of MM, and 3.2% of MMM. Tumor-associated vessels showed the following results: 11 of 19 (58%) in BN, 14 of 21 (67%) in DN, 17 of 23 (74%) in MM, and 6 of 31 (19%) in MMM. A significant loss of expression was noted between MMM and all other lesions in tumor cells and associated vessels. There was no significant difference between BN, DN, and MM. Within primary melanomas, there was a significant correlation between expression of claudin in tumor cells and Clark level/Breslow thickness. Also significant was a decreased expression of claudin in tumor vessels of lesions with higher Breslow thickness or Clark level. These data suggest that loss of claudin-1 may play a significant role in the acquisition of metastatic phenotype in cutaneous melanoma.

Notes: Background:  Fascin containing actin bundles provide mechanical support to cellular protrusions and stress fibers. In cancers, some malignant cells (e.g. subsets of breast and ovarian carcinomas) express fascin. In skin cancer, the role of fascin is unknown.Methods:  Cases of 61 keratocytic neoplasms, 35 melanocytic neoplasms, nine extramammary Paget's disease (four with adenocarcinoma) and five sarcomas (angiosarcoma and atypical fibroxanthoma) were examined by immunohistochemistry, using monoclonal antihuman fascin antibody, clone 55 k-2 (Dako Corporation, Carpinteria, CA, USA).Results:  Fascin labeled all sarcomas and all keratinocytic neoplasms except for pagetoid pattern Bowen's disease. The regions of most intense fascin labeling were seen in the basal cells of infiltrative tumor margins. A minority of Merkel cell carcinomas exhibited weak or absent immunoreactivity. All melanocytic nevi except for some junctional nests of dysplastic melanocytic nevi expressed fascin. However, pagetoid cells of melanoma in situ and epithelioid cells of invasive melanoma weakly expressed or did not express fascin, whereas melanoma cells exhibiting spindle cell morphologies labeled intensely with fascin. Lastly, all cells of extramammary Paget's disease and most associated adenocarcinomas cells did not or were faintly labeled by fascin antibodies. Decreased or absent fascin expression was significantly associated with skin cancers with a high risk for metastasis (e.g. melanoma) vs. those with a low risk (e.g. basal cell carcinoma) (24% vs. 100% with 〉 50% immunoreactivity; p = 0.0001, chi-squared test).Conclusion:  Fascin is expressed by skin tumors that locally infiltrate and replace surrounding tissues indicating a role for fascin in cell adhesion, cell motility and invasiveness. No or weak fascin expression is exhibited by cancers with pagetoid intraepidermal spread and by invasive tumors with a high risk of metastasis. Downregulation or loss of fascin's actin-bundling properties, probably associated with disorganization of cell–cell and cell–matrix contacts, may be a crucial step in the progression from locally invasive to widely disseminating cancers.