title: Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome.
abstract: 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.
authors: Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors: Pieter J A
authors: PJ
authors: de Koning
authors: Niels
authors: N
authors: Bovenschen
authors: Frank K J
authors: FK
authors: Leusink
authors: Roel
authors: R
authors: Broekhuizen
authors: Razi
authors: R
authors: Quadir
authors: Jan T M
authors: JT
authors: van Gemert
authors: Gerrit J
authors: GJ
authors: Hordijk
authors: Wun-Shaing W
authors: WS
authors: Chang
authors: Ingeborg
authors: I
authors: van der Tweel
authors: Marcel G J
authors: MG
authors: Tilanus
authors: J Alain
authors: JA
authors: Kummer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011480:Protease Inhibitors / Q000378:metabolism; D015843:Serpins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D011480:Protease Inhibitors; C530652:SERPINB13 protein, human; D015843:Serpins