Breast cancer cutaneous metastases are associated to uMUC1 and sialyl Lewis x and to highly malignant primary tumors
| Autor: | M. T. Isla Larrain, Amada Segal-Eiras, Martín Enrique Rabassa, Romina Canzoneri, Ariel Osvaldo Zwenger, Ana M. Castro Luna, P. Cabaleiro, Martín Carlos Abba, María Virginia Croce |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine Skin Neoplasms medicine.drug_class Breast Neoplasms Monoclonal antibody Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Antigen Biomarkers Tumor medicine Humans Sialyl Lewis X Antigen skin and connective tissue diseases Cutaneous metastasis MUC1 Aged business.industry Mucin-1 Cell Biology Middle Aged medicine.disease 030104 developmental biology Lymphatic system Sialyl-Lewis X chemistry 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female business |
| Zdroj: | Pathology - Research and Practice. 216:152859 |
| ISSN: | 0344-0338 |
| DOI: | 10.1016/j.prp.2020.152859 |
| Popis: | 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 of200 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. |
| Databáze: | OpenAIRE |
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