No association was GS-1101 found in the subgroup of non adenocarcinoma patients. The reason for the different results in the histological subgroups is un known, however, lung adenocarcinomas have been shown to possess more elastin than squamous cell carcinomas. Since the largest study with 116 adenocarcinoma patients contained only adenocarcinomas, a study bias cannot be excluded. To the best of our knowledge, three other studies ex amined the association Inhibitors,Modulators,Libraries of MME expression and survival in lung cancer. All studies are immunohisto chemical studies. In a study by Kristiansen et al. in 114 NSCLC patients no association of MME immuno staining and survival was found. Only neoplastic cancer cells were evaluated in that study. In a recent study by Ono et al.

on 142 stage I squamous cell lung carcinoma pa tients MME expression was examined in tumor cells and stroma cells separately. Patients with low MME expres sion in stroma or in Inhibitors,Modulators,Libraries tumor cells survived slightly longer, but the differences were not significant. In a study by Gurel et al. MME Inhibitors,Modulators,Libraries expression was studied in tumor cells and stroma cells in 66 patients with NSCLC using immunohistochemistry. In the squamous cell carcinoma subgroup high tumor cell and stroma cell MME expres sion were both associated with poor overall survival. In non squamous cell NSCLC the opposite association was found. No stroma cell MME expression was found in that subgroup. The low number of patients may make the inter pretation of these results difficult. All of these studies were immunohistochemical studies, in contrast to our MME mRNA based survival analysis.

Since MME may be excreted in exosomes, which has been shown e. g. for mesenchymal stem cells, the question arises, Inhibitors,Modulators,Libraries whether MME was excreted and then lost during conventional tissue fixation and immunohisto chemistry. With immunohistochemistry thus the extent of MME expression in cancer tissue may be underestimated. This is supported by the fact that CAFs isolated from all three NSCLCs expressed MME mRNA in our study, while in the studies mentioned above high MME staining in stroma cells was found only in 11% to 19% of cases. This underestimation may partly explain the lack of association between MME expression and worse prognosis in the mentioned studies, as opposed to our mRNA based study. Additional studies examined the expression of MME in combination with other factors and survival.

In the study by Tokuhara et al. 132 NSCLC Inhibitors,Modulators,Libraries patients were grouped according to their tumor MME mRNA and aminopeptidase N mRNA expression. Patients assigned to the group with high MME and low sellckchem aminopeptidase N mRNA showed significantly improved survival. No ana lysis on MME expression alone was performed. Tumor tissue samples were selected to contain primarily cancer cells in that study. In a study by Navab et al.