ABSTRACT
Selective up-regulation of the mRNA of LOXL4, a member of the LOX matrix amine oxidase family, significantly correlated with lymph node metastases and higher tumour stages in head and neck squamous cell carcinomas (HNSCC). To evaluate the diagnostic and prognostic value of the protein we produced an antibody specific for LOXL4 and assessed the expression in 317 human HNSCC specimens. The LOXL4 protein was detected in 92.7% of primary tumours, in 97.8% of lymph node metastases and in affected oral mucosa with high-grade dysplasia, but was absent in various non-neoplastic tissues of the head and neck. TNM categories and overall survival did not link to grades of immunoreactivity. Studies in cultured primary hypopharyngeal HTB-43 carcinoma cells detected perinuclear and cell surface expression of LOXL4, but no nuclear localisation. Therefore, its interactive SRCR-domains and catalytic activity combined with tumour cell specific expression and cell surface associated location indicate multiple functions in tumour cell adhesion and interactions with the extracellular matrix. Our data suggest that LOXL4 is useful both as tumour marker and target in the treatment of HNSCC.
Subject(s)
Amino Acid Oxidoreductases/metabolism , Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/diagnosis , Head and Neck Neoplasms/diagnosis , Cell Line, Tumor , Female , Flow Cytometry , Humans , Immunohistochemistry , Leukoplakia, Oral/diagnosis , Lymphatic Metastasis , Male , Microscopy, Confocal , Middle Aged , Mouth Mucosa/metabolism , Precancerous Conditions/diagnosis , Protein-Lysine 6-OxidaseABSTRACT
BACKGROUND: The impact of codon 72 polymorphism of the human tumour suppressor gene p53 on the risk of developing squamous cell carcinomas of the head and neck (HNSCC) remains unclear because of contradictory results found by several studies. PATIENTS AND METHODS: We genotyped a group of 77 patients with advanced HNSCC by using a direct sequencing method. RESULTS: There were no significant differences in the age of the patients at the time of the first diagnosis nor in the 5-year survival rates. There was no additive effect between different risk factors (alcohol, nicotine) and codon 72 polymorphism. Compared to the frequency of homozygosity encoding for Arg/Arg in the Eurasian population given in literature, the present study has shown a significantly higher frequency of homozygosity for Arg/Arg at codon 72 than commonly detected. CONCLUSION: These findings may indicate codon 72 polymorphism as a risk factor for HNSCC or point to a high variability of codon 72 polymorphism among ethnic groups.
