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

• Published in: International journal of cancer Vol. 125; no. 7; pp. 1542 - 1550
• Main Authors: de Koning, Pieter J.A., Bovenschen, Niels, Leusink, Frank K.J., Broekhuizen, Roel, Quadir, Razi, van Gemert, Jan T.M., Hordijk, Gerrit J., Chang, Wun‐Shaing W., van der Tweel, Ingeborg, Tilanus, Marcel G.J., Kummer, J. Alain
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-10-2009; Wiley-Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms - chemistry; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; HNSCC; Humans; Immunohistochemistry; Loss of Heterozygosity; Lymphatic Metastasis; Male; Medical sciences; Middle Aged; Mouth Neoplasms - chemistry; Mouth Neoplasms - enzymology; Mouth Neoplasms - pathology; Neoplasm Staging; Oropharyngeal Neoplasms - chemistry; Oropharyngeal Neoplasms - pathology; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Predictive Value of Tests; Prognosis; Protease Inhibitors - metabolism; SERPINB13; Serpins - analysis; Serpins - genetics; Serpins - metabolism; Skin Neoplasms - chemistry; Skin Neoplasms - pathology; tumor progression; Tumors; Human; Serpin; Cancerology; Prognosis; HNSCC; Tumor progression; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; SERPINB 13; Malignant tumor; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24507

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. © 2009 UICC