Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome.
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.
de Koning
Pieter J A
PJ
Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Bovenschen
Niels
N
Leusink
Frank K J
FK
Broekhuizen
Roel
R
Quadir
Razi
R
van Gemert
Jan T M
JT
Hordijk
Gerrit J
GJ
Chang
Wun-Shaing W
WS
van der Tweel
Ingeborg
I
Tilanus
Marcel G J
MG
Kummer
J Alain
JA
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
D014408:Biomarkers, Tumor; D011480:Protease Inhibitors; C530652:SERPINB13 protein, human; D015843:Serpins