Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer

In the quest for markers of expression and progression for prostate cancer (PCa), the majority of studies have focussed on molecular data exclusively from primary tumours. Although expression in metastases is inferred, a lack of correlation with secondary tumours potentially limits their applicability diagnostically and therapeutically. Molecular targets were identified by examining expression profiles of prostate cell lines using cDNA microarrays. Those genes identified were verified on PCa cell lines and tumour samples from both primary and secondary tumours using real-time RT–PCR, western blotting and immunohistochemistry. Claudin-4, coding for an integral membrane cell-junction protein, was the most significantly (P<0.00001) upregulated marker in both primary and metastatic tumour specimens compared with benign prostatic hyperplasia at both RNA and protein levels. In primary tumours, claudin-4 was more highly expressed in lower grade (Gleason 6) lesions than in higher grade (Gleason ⩾7) cancers. Expression was prominent throughout metastases from a variety of secondary sites in fresh-frozen and formalin-fixed specimens from both androgen-intact and androgen-suppressed patients. As a result of its prominent expression in both primary and secondary PCas, together with its established role as a receptor for Clostridium perfringens enterotoxin, claudin-4 may be useful as a potential marker and therapeutic target for PCa metastases

Serum cytokines and tumour markers in patients with non-small cell carcinoma of the lung

We compared the serum levels of several cytokines with established tumour markers in 24 patients with non-small cell lung cancer (NSCLC) and 31 patients with benign lung disease (BLD). Cytokine levels were measured using in-house double determinant sandwich ELISAs and tumour markers by a variety of established techniques. There was no correlation between serum cytokines and expression of cytokeratins 18 and 19, MUC1 and carcinoembryonic antigen. While no significant difference was observed in any of the cytokines between patients with NSCLC and BLD, patients with metastatic tumour had a significantly higher level of serum tumour necrosis factor α and interleukin 10 than those with localised disease (P < 0.015 and P < 0.05 respectively). The serum levels of granulocyte macrophage colony stimulating factor and interferon gamma were no different between these groups. These results suggest immunological effects of NSCLC which tends towards impaired cell mediated immunity in patients with metastatic disease

Serum markers CASA, CEA, CYFRA 21-1, MSA, NSE, TPA and TPS in lung cancer

Serum CASA, CEA, CYFRA 21-1, NSE, MSA, TPA, and TPS were determined in patients with lung cancer (LC), benign lung disease (BL), and healthy control (HC) donors. Using predefined cutpoints, the cytokeratin-related markers TPA, TPS, and CYFRA showed the highest sensitivity in non-small cell lung cancer (TPA; 69%, TPS 63%, CYFRA 54%), while NSE gave the highest sensitivity in small cell lung cancer (50%), indicating that these markers may be most appropriate in monitoring the course of disease and the patients response to therapy. Receiver-operator analysis was performed to compare assays at the same specificity. At high specificities (295%), CYFRA was significantly better than all assays except CASA in the LC vs. HC and LC vs. non-infectious BL comparisons (