Breast cancer cutaneous metastases are associated to uMUC1 and sialyl Lewis x and to highly malignant primary tumors |
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| Affiliation: | 1. Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina;2. Laboratorio de Patología, Citopatología e Inmunohistoquímica, Neuquén, Argentina;3. GOCS Neuquén Hospital, Neuquén, Argentina;1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran;2. Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran;4. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;5. Division of Hematology and Transfusion Medicine, Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea;2. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;1. Orthopedic department, Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, China;1. Department of Advanced Biomedical Sciences, Pathology Section, Federico II University of Naples, Naples, Italy;2. Department of Neuroscience, Reproductive Sciences and Dentistry, Ophthalmology Section, Federico II University of Naples, Naples, Italy;3. Department of Clinical Medicine and Surgery, Hematology Section, Federico II University of Naples, Naples, Italy;1. Department of General Surgery, Xiangya Hospital of Central South University, Changsha 410008, PR China;2. Center for Mental Health Services, Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, PR China;1. Respiratory Medicine, Zhejiang Provincial Armed Police Corps Hospital, 304052, Jiaxing, Zhejiang, PR China;2. Wenzhou Medical University, 325035, Wenzhou, Zhejiang, PR China |
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| Abstract: | Breast cancer spreading to different organs have been related to different molecules and mechanisms, but cutaneous metastasis remains unexplored. Increasing evidence showed that MUC1 and some of its carbohydrate associated antigens may be implicated in breast cancer metastasis. In this study we analyzed these tumor markers in order to identify breast cancer cutaneous metastatic profiles. A cohort of 26 primary tumors from breast cancer patients with cutaneous metastases were included; also, cutaneous and lymphatic node metastatic samples and primary tumors from breast cancer patients without metastases were analysed. Immunohistochemical (IHC) studies demonstrated that both underglycosylated MUC1 (uMUC1) and sialyl Lewis x (sLex) to be positively associated with cutaneous metastatic primary tumors (p < 0.05). Notably, a high percentage of tumors with cutaneous metastases were characterized as triple negative and Her2+ tumors (37.5 % and 29 %, respectively). Some discordant results were found between primary tumors and their matched cutaneous metastases. To determine if MUC1 variants may be carriers of carbohydrate antigens, subcellular fractions from a cutaneous metastatic lesion were obtained, immunoprecipitated and analyzed by Western blot. We found that the isolated uMUC1 with a molecular weight of>200 kDa was also the site for binding of anti-sLex MAb; in coincidence, a high correlation of positive IHC expression of both markers was observed. Our findings confirm that breast cancer cutaneous metastases were associated to highly malignant primary tumors and sustain the hypothesis that u-MUC1 and sLe x may drive breast cancer cutaneous metastases. |
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| Keywords: | Breast cancer Cutaneous metastasis uMUC1 sLex |
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