Except for one study for IL 1B 3594 and another for IL 1RN VNTR

MSI status Tumor tissue of 6 patients [You must be registered and logged in to see this link.] displayed MSI. For all of them, 3 and more loci showed nucleotide expansions and they were therefore considered to be MSI H. All six patients were diagnosed for colon cancer. No association of MSI status with gender, age, TNM and grade was observed. Expression of MMR genes Expression levels of 8 MMR genes were successfully an alyzed. Three other MMR genes were excluded from final analyses due to a very low expression and low fluorescence signal. Overall, only EXO1 was differentially expressed in our study group significantly higher mRNA levels were ob served in tumor tissues when compared with adjacent mucosal tissue. After stratifying patients according to the tumor localization, a different pattern for colon and for rectal carcinomas was observed.

Specifically, [You must be registered and logged in to see this link.] significantly higher expression levels of MSH3 gene were observed in colon tu mors when compared to adjacent mucosal tissue. No differ ences in gene expression were observed in rectal tumors when compared to adjacent mucosal tissues. Interestingly, when expression levels of only tumor tis sues with different localization were compared, tumor localized in colon showed significantly increased levels of almost all analyzed MMR genes, namely MSH2. Although less robust, the same tendency was also observed in the adja cent mucosal tissue for MSH2 and PMS2 genes. Further stratification fo left and right colon did not show any differences. The expression pattern of investigated MMR genes was irrespective of other clinical features.

The only exception was for PMS2 gene in colon tumors, where patients with the pTNM stage I II had significantly lower expression levels than those with pTNM III IV. No difference was observed when pa tients were stratified for any of the considered demo graphic factors. Ten patients with rectal cancer received neo adjuvant therapy before surgery. However, [You must be registered and logged in to see this link.] none of the analyzed genes differed in the expression levels among rectal cancer patients irrespectively of the neoadjuvant therapy. Relationships of expression levels among different MMR genes MMR genes positively correlated between each other in both tumor and adjacent mucosal tissues. Similarly to cancer tissues, in adjacent mucosal tissues, MLH3 correlated with PMS1 and PMS2, but, additionally, MLH3 also correlated with MSH6. In addition, MSH2 again correlated with MSH6.

Concerning the EXO1, in adjacent mucosal tissue the gene strongly cor related with MLH3, MSH6 and PMS1. Promoter methylation of MMR genes The promoter methylation status was analyzed only in those genes whose expression analyses were successfully conducted. Therefore, methylation levels of promoter re gions of EXO1, MLH1, MLH3, PMS1, PMS2, MSH2, MSH3, and MSH6 genes were evaluated in DNA from tumor and adjacent mucosal tissues of 53 CRC patients. Methylation of promoter region was detected only in MLH1. For this gene, a fragment of 100 bp length containing 8 CpG sites was analyzed. Five tumors and two samples from adjacent mucosal tissues exhibited methylated MLH1 promoter re gion. In patients, where normal tissues presented MLH1 promoter methylation, tumor tissue also exhibited pro moter methylation.