Genetic testing in colorectal cancer

Abstract

Introducing the microsatellite instability (MSI) determination as an initial screening test for colorectal cancer (CRC) enables the molecular detection of Lynch syndromes in large populations. The Revised Bethesda guidelines, MsPath model and MSI histology are useful tools for selecting patients for MSI testing. In our investigation, most clinicopathologic characteristics of MSI-H lesions of Serbian patients are similar to those reported in previous studies. CRCs with extent mucin production and localisation in right colon often show MSI. Also, we conclude that MSI-H CRC have better prognosis. Moreover, BRAF gene mutation in MSI-H CRC indicated on sporadic form of CRC with poorer survival and higher recurrence rate than MSI-H tumours without this mutation. Another genetic testing that uses to distinguish sporadic and inherited CRC is methylation of MLH1 gene promoter. These genetic tests (MSI, BRAF, methylation status of MLH1 gene) are important in recognizing Lynch syndrome, while intensive screening for colonic and extracolonic malignances is required for MisMatch Repair gene mutation carriers. Our group assessed the impact of combined prognostic significance of MSI and postoperative 5-FU treatment status on the survival of unselected patients who were treated surgically for CRC in stage II and III and found out that disease free survival was statistical significantly lower in patients with MSI-H CRCs who were treated by adjuvant 5-FU therapy. As novel microsatellite marker, we propose HSP110T17. Antiapoptotic effect increases cell sensitivity to anticancer agent such as oxaliplatin and 5-fluorouracil in CRCs with unstable HSP110T17. Understanding key steps in the oncogenic pathways for CRC may help in the development of new screening markers with the aim to improve the therapy and prognosis of CRC.