In clear cell renal selleck kinase inhibitor cell carcinoma, Ep-CAM expression is infrequent, but patients with Ep-CAM overexpressing tumours show a trend to better survival (Kim et al, 2004; Seligson et al, 2004; Went et al, 2005). A similar correlation was reported for gastric cancers (Songun et al, 2005). Very little information is currently available with regard to the correlation of Ep-CAM expression with survival and tumour staging for colon and lung cancers, while more recent studies have explored larger sample numbers of gastric (Songun et al, 2005) and prostate cancers (Poczatek et al, 1999; Zellweger et al, 2005) for Ep-CAM expression. Due to its frequent and high-level expression, Ep-CAM was selected as target antigen for a multitude of immunotherapeutic approaches (Balzar et al, 1999).
These include murine and human monoclonal antibodies, antibody conjugates with bacterial toxins and chemotherapeutics, and vaccines. Currently, a number of Ep-CAM-specific immunotherapies are in phase I and II clinical trials. These are anti-Ep-CAM antibodies ING-1 (de Bono et al, 2004), adecatumumab (Naundorf et al, 2002; Prang et al, 2005), and edrecolomab (Himmler et al, 2003), as well as an immunotoxin (Zimmermann et al, 1997; Di Paolo et al, 2003). It is therefore very important to understand which human cancers are amenable to Ep-CAM-specific immunotherapy based on Ep-CAM expression with respect to intensity, frequency and disease stage. Likewise, it is interesting to investigate a correlation of Ep-CAM expression with survival prognosis in patients.
The aim of the present retrospective study was to investigate the frequency and intensity of Ep-CAM expression in four major human cancers by the use of tissue microarrays. This technology allows for a simultaneous comparison of immunohistochemical staining patterns and intensities across a large panel of tumour samples. Variability due to fixation and staining procedures are reduced to a minimum, AV-951 while comparability is maximised. Epithelial cell adhesion molecule expression results were correlated for the first time with clinico-pathological parameters in colon and lung cancers, while results from a large panel of gastric and prostate cancer samples are being compared to published data. Our results show that colon, gastric and prostate cancers as well as adenocarcinoma of the lung are promising indications for treatment with Ep-CAM-specific immunotherapies. Their frequencies of high-level Ep-CAM expression >80% may even obviate the need for prescreening of patients. MATERIALS AND METHODS Array composition Primary tumours of colon, stomach, lung and prostate were included in this study.