Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 17;69(7):e20230371.
doi: 10.1590/1806-9282.20230371. eCollection 2023.

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

Tugce Bolme Savli  1 , Husniye Esra Pasaoglu  2 , Taha Cumhan Savli  3 , Ali Muhammedoglu  2 , Merve Tokocin  4 , Çiğdem Öztürk  5
Affiliations

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

Tugce Bolme Savli et al. Rev Assoc Med Bras (1992). .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: the authors declare there is no conflicts of interest.

Figures

Figure 1.
Figure 1.. CD44 positivity in the tumor (CD44, 200´ magnification).
Figure 2.
Figure 2.. Cytotoxic T lymphocyte-associated antigen 4 evaluation according to the percentage of staining in lymphocytes around the tumor bud 13% (cytotoxic T lymphocyte-associated antigen 4, 400´ magnification).
See this image and copyright information in PMC

References

    1. Lugli A, Zlobec I, Berger MD, Kirsch R, Nagtegaal ID. Tumour budding in solid cancers. Nat Rev Clin Oncol. 2021;18(2):101–15. doi: 10.1038/s41571-020-0422-y. - DOI - PubMed
    1. Zhang Y, Weinberg RA. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front Med. 2018;12(4):361–73. doi: 10.1007/s11684-018-0656-6. - DOI - PMC - PubMed
    1. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991;251(5000):1451–5. doi: 10.1126/science.2006419. - DOI - PubMed
    1. McFarlane S, McFarlane C, Montgomery N, Hill A, Waugh DJ. CD44-mediated activation of α5β1-integrin, cortactin and paxillin signaling underpins adhesion of basal-like breast cancer cells to endothelium and fibronectin-enriched matrices. Oncotarget. 2015;6(34):36762–73. doi: 10.18632/oncotarget.5461. - DOI - PMC - PubMed
    1. Chen B, Li X, Wu L, Zhou D, Song Y, Zhang L, et al. Quercetin suppresses human glioblastoma migration and invasion via GSK3β/β-catenin/ZEB1 signaling pathway. Front Pharmacol. 2022;13:963614. doi: 10.3389/fphar.2022.963614. - DOI - PMC - PubMed