AbstractsBiology & Animal Science


by Tuomas Kaprio

Institution: University of Helsinki
Department: Institute of Clinical Medicine, Department of Surgery; Department of Pathology, University of Helsinki, Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland
Year: 2015
Keywords: lääketiede
Record ID: 1130528
Full text PDF: http://hdl.handle.net/10138/154162


Background and aims Colorectal cancer (CRC) is one of the world s three most common cancers, and its incidence is rising. Novel biomarkers are essential for diagnostic and prognostic tools and to identify patients for targeted and individualized therapy. Covering all human cells, the carbohydrate units of glycoproteins, glycolipids, and proteoglycans are glycans. Carcinoma-related glycan structures are potential cancer biomarkers, since glycosylation evolves during carcinogenesis. Suggested to play a role in carcinogenesis are glycoproteins podocalyxin (PODXL) and regenerating islet-derived gene (REG) 4. PODXL s aberrant expression or allelic variation or both associate in different cancers with poor prognosis and unfavourable clinicopathological characteristics. Up-regulated REG4 expression occurs in inflammatory bowel diseases and also in gastrointestinal cancers. Reports on the association of REG4 expression with CRC prognosis have been mixed, however. Material and Methods Comparison of the N-glycan profiles of 5 rectal adenomas and 18 rectal carcinomas of different stages was by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Tumour expression of REG4 and PODXL was evaluated by immunohistochemistry in 840 consecutive CRC patients surgically treated between 1983 and 2001. In addition we evaluated in a subgroup of 220 consecutively surgically treated CRC patients the tumour expression of MUC1, MUC2, MUC5AC, synapthophysin, chromogranin, sialyl Lewis a (sLea), and pauci-mannose. All patients were treated at Helsinki University Hospital (HUH). Results Rectal adenomas and carcinomas can be distinguished from one another based on their N-glycosylation profile. Differences in N-glycosylation existed also between carcinomas of different stages. Based on these results pauci-mannose and sLea were chosen for immunohistochemical analysis: in CRC sLea correlated with poor prognosis, and in advanced CRC, pauci-mannose expression correlated with poor prognosis. PODXL was an independent marker of poor prognosis in CRC. The two antibodies showed similar prognostic profiles, but their staining patterns differed, and they recognized different groups of patients with a poor prognosis. Combination of the two PODXL antibodies identified a group of patients with even worse prognosis. REG4 expression associated with MUC1, MUC2, and MUC5AC expression in CRC and was a marker of favourable prognosis in non-mucinous CRC. Conclusion Mass spectrometry identified several carcinoma-related glycans and a method of transforming these results into immunohistochemistry was demonstrated. PODXL was a marker of poor prognosis in CRC, whereas REG4 expression predicted a favourable prognosis in non-mucinous CRC. Paksu- ja peräsuolensyöpä on yksi maailman kolmesta yleisimmästä syövästä ja sen esiintyvyys on kasvussa. Hoitojen yksilöimiseksi ja paremmaksi kohdentamiseksi tarvitaan uusia biomarkkereita. Väitöskirjassa tutkittiin kahden eri glykoproteiinin, podokalyksiinin ja REG4, vaikutusta paksu- ja…