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Annexin A1 subcellular expression in laryngeal squamous cell carcinoma
V A F Alves1, S Nonogaki, P M Cury
1Department of Pathology, School of Medicine, USP, São Paulo, Brazil.
Aims:
Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis.
Methods And Results:
Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis.
Conclusions:
ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.
Insights
Annexin A1 (ANXA1) expression decreases in laryngeal squamous cell carcinoma (LSCC). This ANXA1 down-regulation occurs early in laryngeal carcinogenesis and involves ANXA1 migration from the nucleus to the membrane.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Annexin A1 (ANXA1) is a protein involved in cytoskeletal organization and cell differentiation, particularly in inflammatory and neoplastic processes.
- ANXA1 exhibits dynamic subcellular localization, moving between cytoplasm, membranes, nucleus, and extracellular space, influenced by signaling pathways.
- Its role in laryngeal carcinogenesis is not fully understood.
Purpose of the Study:
- To investigate the subcellular expression patterns of ANXA1 in neoplastic and non-neoplastic laryngeal tissues.
- To elucidate the specific role of ANXA1 in the process of laryngeal carcinogenesis.
- To correlate ANXA1 expression patterns with clinicopathological features of laryngeal squamous cell carcinoma (LSCC).
Main Methods:
- Gene expression analysis to compare ANXA1 levels in LSCC and normal tissues.
- Quantitative polymerase chain reaction (qPCR) to confirm ANXA1 gene expression.
- Immunohistochemical analysis of ANXA1 subcellular localization in 241 LSCC samples from 95 patients.
Main Results:
- Reduced ANXA1 gene expression was detected in LSCC compared to non-neoplastic margins.
- ANXA1 expression was found to be down-regulated in dysplastic, tumorous, and metastatic lesions.
- A progressive shift of ANXA1 localization from the nucleus to the cell membrane was observed during laryngeal tumorigenesis.
Conclusions:
- ANXA1 dysregulation is an early event in laryngeal carcinogenesis, evident even in intra-epithelial neoplasms.
- The observed down-regulation and subcellular redistribution of ANXA1 are significant in the early stages of laryngeal cancer development.
- ANXA1 expression levels were not found to be associated with prognostic parameters like nodal metastasis.
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