Research Article High Percentage of ADAM-10 Positive Melanoma Cells Correlates with Paucity of Tumor-Infiltrating Lymphocytes but Does Not Predict Prognosis in Cutaneous Melanoma Patients Piotr Donizy, 1 Marcin Zietek, 2 Marek Leskiewicz, 3 Agnieszka Halon, 1 and Rafal Matkowski 2,4 1 Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland 2 Lower Silesian Oncology Centre, pl. Hirszfelda 12, 53-413 Wroclaw, Poland 3 Department of Statistics, Wroclaw University of Economics, Komandorska 118-120, 53-345 Wroclaw, Poland 4 Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, pl. Hirszfelda 12, 53-413 Wroclaw, Poland Correspondence should be addressed to Piotr Donizy; piotrdonizy@wp.pl Received 8 April 2015; Revised 6 July 2015; Accepted 8 July 2015 Academic Editor: Francesco A. Mauri Copyright © 2015 Piotr Donizy et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ADAM-10 (CDw156, CD156c, and kuzbanian) is a protein belonging to a superfamily of metalloproteases, enzymes capable of degrading the extracellular matrix. ADAMs have also been shown to be primarily involved in ectodomain cleavage. he aim of the study was to assess the expression and intracellular location of ADAM-10 in 104 primary skin melanomas and 16 metastatic lesions from regional lymph nodes. Also, prognostic signiicance of ADAM-10 expression in primary tumor cells and metastatic lesion cells was evaluated during 5-year observation. It was revealed that high expression of ADAM-10 positive cells was strictly related with lower intensity of tumor-iniltrating lymphocytes ( = 0.037), which suggests that ADAM-10 regulates immunoresponse in melanoma initiation and progression. No statistically signiicant correlations were found between ADAM-10 expression in primary tumor cells and nodal metastases and other histopathological parameters analyzed. Decreased immunoreactivity of ADAM-10 in cancer cells from regional lymph nodes was correlated with worse prognosis; however this correlation was statistically nonsigniicant ( = 0.065). Review of the literature shows that our study is the irst one ever to describe the signiicance of ADAM- 10 expression in correlation with detailed histopathological parameters of the primary tumor and data on long-term survival of cutaneous melanoma patients. 1. Introduction ADAM-10 (CDw156, CD156c, and kuzbanian) is a protein belonging to a superfamily of metalloproteases, enzymes ca- pable of degrading the extracellular matrix. ADAMs have also been shown to be primarily involved in ectodomain cleavage [1]. ADAM family proteins are membrane anchored glyco- proteins which play a major role in a number of cytobiochem- ical processes such as proteolysis, intercellular adhesion, and activation of various signaling cascades [2, 3]. he analysis of the molecular structure of ADAMs showed that they exhibit a few characteristic domains which, starting from their N-terminal ends, include a prodomain, a metallopro- tease domain, a disintegrin-like domain, EGF-like domain, a cysteine-rich domain, and transmembrane and cytoplasmic fragments [4]. In a normal cell, catalytically active ADAM-10 protein functions as an enzyme shedding extracellular fragments of membrane-bound proteins (shedding), which leads to the release of active protein ectodomains. ADAM-10 also par- ticipates in the biochemical process referred to as regulated intramembrane proteolysis (RIP), during which, and with mediation by presenilin-dependent -secretase, intracellular domain (ICD) fragments are formed, which upon translo- cation to the nucleus modulate several signal transduction pathways and become either transcriptional activators or repressors [5, 6]. A wide spectrum of protein substrates for ADAM-10 includes molecules that have been shown to be involved in carcinogenesis initiation and cancer progression. Hindawi Publishing Corporation Analytical Cellular Pathology Volume 2015, Article ID 975436, 7 pages http://dx.doi.org/10.1155/2015/975436