A cohort study of sex differences and prognostic biomarkers in colerctal cancer

Accumulating evidence indicates that CRC is a heterogeneous disease, which affects outcome beyond what can be predicted by disease stage and other conventional prognostic factors. Thus, there is a great need to identify new biomarkers to enable a more accurate prognostication, and to help select patients for adjuvant treatment. In this thesis, the associations of a series of putative biomarkers with survival, treatment response and clinicopathological factors were investigated in a large cohort of incident CRC, with special attention to sex differences. Tumours from 557 incident cases of CRC, assembled in tissue microarrays, were evaluated for expression of cyclin D1, mismatch repair proteins, beta-catenin and epidermal growth factor receptor (EGFR) by immunohistochemistry, and further, EGFR gene copy number (GCN) alterations by brightfield double-in situ hybridization. In addition, KRAS and BRAF mutational status was assessed by pyrosequencing. The results demonstrate several relevant associations of the investigative biomarkers with prognosis and treatment response in CRC. Moreover, substantial sex differences in the clinicopathological correlates and prognostic significance of some of the biomarkers were observed.