Expression of cytotoxic T lymphocyte-associated antigen 4, CD44, and E-cadherin in the microenvironment of breast carcinomas

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Savli T. B., Pasaoglu H. E., Savli T. C., Muhammedoglu A., Tokocin M., Öztürk Ç.

Revista da Associacao Medica Brasileira, vol.69, no.7, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 69 Issue: 7
  • Publication Date: 2023
  • Doi Number: 10.1590/1806-9282.20230371
  • Journal Name: Revista da Associacao Medica Brasileira
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Breast neoplasms, CD44 protein, CTLA-4 antigen, E-cadherin, mouse, Tumor microenvironment
  • Recep Tayyip Erdoğan University Affiliated: Yes


OBJECTIVE: The expression of cytotoxic T lymphocyte-associated antigen 4, E-cadherin, and CD44 in the area of tumor budding was investigated in breast carcinomas in our study. METHODS: Tumor budding was counted at the invasive margins in 179 breast carcinomas. To understand the microenvironment of tumor budding, we examined the expression status of the immune checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4, E-cadherin, and CD44. RESULTS: Tumors were separated into low (≤5) and high tumor budding groups (>5) based on the median budding number. Lymphovascular, perineural invasion, and the number of metastatic lymph nodes were significantly higher in high-grade budding tumors (p=0.001, p<0.001, and p=0.019, respectively). Tumor-infiltrating lymphocytes were significantly higher in tumors without tumor buddings (p<0.001). When the number of budding increases by one unit, overall survival decreases by 1.07 times (p=0.013). Also, it increases the risk of progression by 1.06 times (p=0.048). In high tumor budding groups, the cytotoxic T lymphocyte-associated antigen 4 staining percentage of lymphocytes was significantly higher (p=0.026). With each increase in the number of buds, an increase in the percentage of cytotoxic T lymphocyte-associated antigen 4 staining was seen in lymphocytes in the microenvironment of TB (p=0.034). CONCLUSION: Tumor budding could predict poor prognosis in breast carcinomas, and anti-cytotoxic T lymphocyte-associated antigen 4 immunotherapies may be beneficial in patients with high tumor budding tumors.