Coexpression of hypoxia-inducible factor-1a and glucose transporter-1 is associated with poor prognosis in oral squamous cell carcinoma patients Aims: To study whether coexpression of the two hypoxia-related proteins hypoxia-inducible factor (HIF)-1a and glucose transporter (GLUT)-1 has prognostic relevance in oral squamous cell carcinomas (OSCCs). Methods and results: Eighty-two OSCC samples were analysed for expression levels of HIF-1a and GLUT-1 by immunohistochemistry. Protein expression was assessed with an immunoreactive score system, and the correlations between gene expression and both clinical and pathohistological parameters were examined. Overexpression of either GLUT-1 or HIF-1a was associated with poor disease-specific survival in OSCC patients. Multivariate Cox proportional-hazards regression analysis revealed that increased expression of HIF-1a was significantly associated with disease-specific survival (relative risk = 3.24, P = 0.024), as compared with the group with a low level of expression. Coexpression of HIF-1a and GLUT-1 was additively and significantly associated with adverse prognoses in patients with OSCC. Patients whose tumours had increased levels of expression of both HIF-1a and GLUT-1 were found to have a 5.13-fold increased risk of tumour-related death (P = 0.017). Conclusions: Coexpression of high levels of HIF-1a and GLUT-1 is significantly correlated with prognosis in OSCC patients, suggesting that the coexpression of these proteins can be used as both an early diagnostic and independent prognostic marker.

Purpose: The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood (so-called circulating tumor cells) for renal cell carcinoma patients. Methods: Two hundred thirty-three peripheral blood samples from 154 renal cell carcinoma patients were investigated for the presence of disseminated tumor cells by autoMACS technique and immunocytochemical staining of cytokeratin. The frequency of circulating tumor cells was analyzed statistically for correlation with relevant clinical data. Results: Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+) and cells without a detectable cytokeratin expression, which we called large blue-stained cells with a tumorlike morphology. After following the CD45 autoMACS depletion protocol, we identified circulating tumor cells in 96 (41%) of 233 peripheral blood samples, which originated from 81 (53%) of 154 renal cell carcinoma patients.A significant correlation between the detection of circulating tumor cells and positive lymph node status (P < 0.001; χ 2 test) and the presence of synchronous metastases at the time of primary tumor resection (P = 0.014; χ 2 test) was found. In a multivariate Cox's regression hazard model, presence of CK+ circulating tumor cells was significantly correlated with poor overall survival for renal cell carcinoma patients (relative risk, 2.3; P = 0.048). Conclusions:The presence of circulating tumor cells correlated to lymph node status and presence of synchronous metastases in renal cell carcinoma. It is important to evaluate CK+ and blue-stained tumor cells together to determine the role of circulating tumor cells in tumor behavior and disease progression. Detection of CK+ circulating tumor cells in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2190-4)

A co-detection of low Hif1alpha/CAIX expression is significantly correlated with a better prognosis for OSCC patients, which may have implications for therapy options for these patients.

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