Dataset Information

Ursodeoxycholic Acid (UDCA) in Preventing Hepatobiliary and Colorectal Malignancy in Surveillance Patients with Primary Sclerosing Cholangitis (PSC)

ABSTRACT: Primary objectives: (i) To assess in incidence of biliary malignancy as assessed by surveillance MR/MRCP in patients with PSC with and without response to UDCA(ii) To assess in incidence of colorectal malignancy as assessed by surveillance colonoscopy in patients with PSC with and without response to UDCA Primary endpoints: - any hepatobiliary malignancy including low-grade dysplasia detected by surveillance MRCP- any colorectal malignancy including low-grade dysplasia detected by surveillance colonoscopy

DISEASE(S): Primary Sclerosing Cholangitis With Or Without Concomitant Inflammatory Bowel Disease Included In An Unlimited Surveillance Program For Hepatobiliary And Colorectal Malignancy

PROVIDER: 2534809 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN. Experimental Design: Laser capture microdissection was used to isolate distinct foci of low grade, moderate grade, high grade, and invasive IPMN from paraffin embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used for gene expression analysis to compare low and moderate grade (LMD) IPMN to high grade and invasive (HgInv) IPMN. Results: When comparing samples of LMD dysplasia (n=15) to those demonstrating HgInv (n=13), 62 genes were identified as showing significant changes in expression (p≤0.05 and a 2-fold cutoff), with up-regulation of 41 in HgInv IPMN and down-regulation in 21. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial to mesenchymal transition. Hierarchical clustering analysis demonstrated the ability of these 62 differentially expressed genes to distinguish between LMD and HgInv samples. In addition, altered signaling in several TGFβ-related pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection. Using laser capture microdissection, distinct foci of low (n=10), moderate (n=5), and high grade dysplasia (n=6) as well as invasive carcinoma (n=7) were isolated from paraffin embedded archival tissue of 14 patients who underwent resection for IPMN. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare low and moderate grade IPMN to high and invasive IPMN.

Dataset Information

Ursodeoxycholic Acid (UDCA) in Preventing Hepatobiliary and Colorectal Malignancy in Surveillance Patients with Primary Sclerosing Cholangitis (PSC)

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