Association between soluble MICA levels and disease stage IV oral squamous cell carcinoma in Japanese patients.

The soluble form of major histocompatibility complex class I-related chain A (MICA) is released from the surface of tumor cells of epithelial origin. Although MICA expressed on the cell surface stimulates the immunoreceptor natural killer (NK) group 2, member D (NKG2D), the secreted form downregulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between serum levels of soluble MICA and the severity of disease in patients with oral squamous cell carcinoma (OSCC). We used enzyme-linked immunoabsorbent assay to measure serum levels of soluble MICA in OSCC patients and normal control individuals. Among patients categorized according to most disease parameters tested (tumor size, location, grade of differentiation, regional lymph node status, disease stage), soluble MICA levels in sera did not statistically differ from those in normal control individuals. Patients with stage IV disease and/or regional lymph node metastasis did, however, exhibit significantly higher serum levels of soluble MICA than control individuals (95% confidence interval (CI), 0.65-2.45, p = 0.021, and 95% CI, 0.62-4.42, p = 0.031, respectively). Overall survival rates were significantly higher for OSCC patients with low soluble MICA levels (<50 pg/ml) than for those with high soluble MICA levels (>50 pg/ml) (95% CI, 0.43-2.75, p = 0.03). Serum levels of soluble MICA may be useful in the diagnosis of advanced stage OSCC and as an indicator of regional lymph node metastasis.

An association between the MICA-A5.1 allele and an increased susceptibility to oral squamous cell carcinoma in Japanese patients.

BACKGROUND: Recently, a new polymorphic gene family called the major histocompatibility complex class I chain-related gene A (MICA) was discovered about 40 kb centromeric to HLA-B gene. The MICA protein, expressed on epithelial cells and many kinds of tumor cells, serves to regulate immune function. The MICA protein is thought to activate immune function on mucosal tissue by binding to NKG2D which is expressed on most natural killer cells, CD8 positive T cells, and gamma delta T cells. An association between MICA gene polymorphisms and the development of oral squamous cell carcinoma (OSCC) has also been reported. OBJECTIVE: This study was designed to test this association in Japanese patients with OSCC. METHODS: The (GCT)(n) polymorphisms of the MICA gene was investigated in 123 patients with OSCC and 188 normal controls using polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis. RESULTS: Five alleles, namely A4, A5, A6, A9, and A5.1, were found in both groups. The phenotype frequency of the MICA-A5.1 allele was significantly higher in patients with OSCC when compared with normal controls (OR 1.707, 95% CI 0.76-3.45, P=0.042). Also, the microsatellite frequency of the MICA-A5.1 allele was significantly higher in patients with OSCC compared with normal controls (OR 1.664, 95% CI 0.82-3.42, P=0.021). Lastly, the frequency of the MICA-A5.1 allele was significantly higher in those with lymph node metastasis from OSCC compared with normal controls (OR 2.605, 95% CI 1.14-5.27, P=0.026). CONCLUSIONS: These results suggest that the MICA-A5.1 allele may be associated with an increased susceptibility to OSCC in Japan.