Down-regulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome

[[abstract]]Introduction: Tumorigenesis of head and neck squamous cell carcinomas (HNSCC) is associated with various genetic changes, including loss of heterozygosity (LOH) of chromosome 18q21. This chromosomal region maps a cluster of human intracellular serine protease inhibitors (serpins), including SERPINB13. Down-regulation of SERPINB13 expression in HNSCC has been demonstrated on both mRNA and protein levels. The aim of the present study was to investigate if down-regulated SERPINB13 protein expression in HNSCC correlates with histopathological and clinical parameters of these tumors and with patient survival. Methods: For this purpose we developed SERPINB13-specific antibodies and SERPINB13 expression was studied by immunohistochemistry in a well-defined cohort of 99 HNSCC of the oral cavity and oropharynx. Results: SERPINB13 expression was partially or totally down-regulated in 75% of the HNSCC as compared with endogenous expression in non-neoplastic epithelial cells. LOH of the SERPINB13 gene in these HNSCC was a major cause of the down-regulated SERPINB13 protein expression. Down-regulation of SERPINB13 expression in HNSCC correlated significantly with 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. Conclusion: This is the first report demonstrating that downregulation of SERPINB13 protein expression in HNSCC is positively associated with poor clinical outcome. Therefore, SERPINB13 may act as an important protease inhibitor involved in the progression of HNSCC