Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer death. Overall CRC is a heterogenous disease with major differences in outcome and therapeutic response. Genomic and gene expression profiles stratify CRC tumors into several distinct molecular subtypes, which affect prognosis and predict response to surgical and oncological treatments. Microsatellite instability (MSI) is a hypermutable phenotype caused by a deficiency in the DNA mismatch repair (MMR) machinery. MSI is detected in approximately 15% of all CRC cases, of which 10-14% represent sporadic (acquired i.e. non-hereditary) hypermethylation of the MMR gene MLH1 promoter. About 1-5% of MSI CRC patients, in turn, suffer from Lynch syndrome (LS) caused by a germline mutation in one of the MMR genes MLH1, MSH2, MSH6, or PMS2. The recent international guidelines, i.e. UICC TNM classification (2017) and WHO Classification of Tumors (Digestive System Tumors, 5th Edition, 2019), recommend MSI testing of all newly diagnosed CRC cases, and in Helsinki University Hospital universal MSI screening of CRC patients started in January 2018. Our science project consists of development of CRC patient diagnostics and identification of novel diagnostic methods to aid CRC patient follow-up and treatment.
Pseudomyxoma peritonei (PMP) is a rare malignant disease (3-4 cases per million per year) that most often originates from the appendix and presents as a mucinous adenocarcinoma growing in the peritoneal cavity. The abundance of mucinous ascites secreted by the more common low-grade (LG) subtype of PMP leads to progressive obstruction, which is eventually fatal. In addition to mucin production, the high-grade (HG) subtype of PMP is able to invade surrounding tissues and organs, thereby shortening the survival time when compared to the LG disease. We have analyzed the mutational profile of PMP and found KRAS mutation to be frequent and nearly always combined with mutated GNAS or other component of the cAMP-PKA signaling pathway. Further, we have identified CEA and EpCAM proteins to be ubiquitously expressed in PMP cells, thus serving as immunohistochemistry markers to detect disseminated PMP cells. We have a representative series of over one hundred formalin-fixed, paraffin-embedded (FFPE) PMP tissue specimens. In PMP research, we participate in the COST Action CA17101, European Network on Pseudomyxoma Peritonei.