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Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome
Author(s) -
de Koning Pieter J.A.,
Bovenschen Niels,
Leusink Frank K.J.,
Broekhuizen Roel,
Quadir Razi,
van Gemert Jan T.M.,
Hordijk Gerrit J.,
Chang WunShaing W.,
van der Tweel Ingeborg,
Tilanus Marcel G.J.,
Kummer J. Alain
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24507
Subject(s) - head and neck squamous cell carcinoma , downregulation and upregulation , cancer research , immunohistochemistry , carcinogenesis , biology , pathology , tumor progression , head and neck cancer , medicine , cancer , oncology , gene , biochemistry
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