Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome

Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
International Journal of Cancer (Impact Factor: 5.09). 10/2009; 125(7):1542-50. DOI: 10.1002/ijc.24507
Source: PubMed


Tumorigenesis of head and neck squamous cell carcinomas (HNSCC) is associated with various genetic changes such as loss of heterozygosity (LOH) on human chromosome 18q21. This chromosomal region maps a gene cluster coding for a family of intracellular serine protease inhibitors (serpins), including SERPINB13. As SERPINB13 expression in HNSCC has recently been shown to be downregulated both at the mRNA and protein levels, here we investigated if such a low SERPINB13 expression is associated with histopathological and clinical parameters of HNSCC tumors and patient survival. By generating specific antibodies followed by immunohistochemistry on a well-defined cohort of 99 HNSCC of the oral cavity and oropharynx, SERPINB13 expression was found to be partially or totally downregulated in 75% of the HNSCC as compared with endogenous expression in non-neoplastic epithelial cells. Downregulation of SERPINB13 protein expression in HNSCC was significantly associated with the presence of LOH at the SERPINB13 gene in the tumors (p = 0.006), a poor differentiation grade of the tumors (p = 0.001), the presence of a lymph node metastasis (p = 0.012), and a decreased disease-free (p = 0.033) as well as overall (p = 0.018) survival of the patients. This is the first report demonstrating that downregulation of SERPINB13 protein expression in HNSCC is positively associated with poor clinical outcome. Therefore, SERPINB13 seems to act as an important protease inhibitor involved in the progression of HNSCC.

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Available from: Marcel G.J. Tilanus, Mar 25, 2015
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    • "Also, extracellular presence of headpin reduce invasion, migration, and tube formation of endothelial cells, and when headpin is located at nucleus, it is able to regulate the transcription of mediators of cell proliferation [166]. The down-regulation of headpin gene by means of hypermethylation is linked with the development, aggressiveness and poor clinical outcome of oral, head and neck squamous cell carcinomas [167] [168]. Kallistatin or kallikrein-binding protein (KBP) is a serpin firstly discovered as an inhibitor of the kininogenase and amidolytic activities of tissue kallikrein in vitro with [169]. "
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