Alves V A F, Nonogaki S, Cury P M, Wünsch-Filho V, de Carvalho M B, Michaluart-Júnior P, Moyses R A, Curioni O A, Figueiredo D L A, Scapulatempo-Neto C, Parra E R, Polachini G M, Silistino-Souza R, Oliani S M, Silva-Júnior W A, Nobrega F G, Tajara E H, Zago M A
Department of Pathology, School of Medicine, USP, São Paulo, Brazil.
Histopathology. 2008 Dec;53(6):715-27. doi: 10.1111/j.1365-2559.2008.03186.x.
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.
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.
ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.
膜联蛋白A1(ANXA1)是一种可溶性细胞质蛋白,当钙水平升高时会转移至细胞膜。研究还表明,根据酪氨酸激酶信号传导情况,ANXA1也会转移至细胞核或细胞外,从而干扰细胞骨架组织和细胞分化,这一现象主要发生在炎症和肿瘤形成过程中。本研究旨在调查喉鳞状细胞癌(LSCC)患者肿瘤和非肿瘤样本中ANXA1免疫组化表达的亚细胞模式,以阐明ANXA1在喉癌发生中的作用。
基因表达实验的系列分析检测发现,与相应的非肿瘤边缘组织相比,LSCC中ANXA1基因表达降低。定量聚合酶链反应证实了15例LSCC和8例匹配的正常样本中ANXA1表达较低。因此,我们研究了95例LSCC患者的241份石蜡包埋样本中ANXA1免疫组化表达的亚细胞模式。结果显示,发育异常、肿瘤和转移病变中ANXA1表达下调,并为喉肿瘤发生过程中ANXA1从细胞核向细胞膜的逐步迁移提供了证据。
在喉癌发生早期的上皮内肿瘤中观察到ANXA1失调;未发现其与预后参数(如淋巴结转移)相关。