|β-catenin expression in relation to genetic instability and prognosis in colorectal cancer|
Authors: Ann Mårtensson, åke öberg, Andreas Jung, Kristina Cederquist, Roger Stenling, Richard Palmqvist
Department of Medical Biosciences, Pathology, Umeå University, SE-901 85 Umeå, Sweden
In the carcinogenesis of colorectal cancer (CRC) genetic instability and dysfunction of the Wnt-signalling pathway play important roles. Most Wnt-signalling dysfunctions lead to the nuclear accumulation of β-catenin. The aim of the present study was to investigate whether nuclear accumulation of β-catenin is associated with prognosis and genetic instability. We used immunohistochemistry to study nuclear β-catenin expression in 67 CRCs. The expression was evaluated in the entire tumour section as mean values and in tumour budding at the invasive margin. We compared the results with chromosomal and microsatellite instability (CIN vs. MSI), p53 accumulation, and clinicopathological variables including survival. The nuclear accumulation of β-catenin was significantly associated with abnormal p53 expression and aneuploidy, typically for CIN, whereas no tumour with nuclear β-catenin expression at the invasive margin displayed MSI. The β-catenin expression pattern did not correlate significantly with CRC patient prognosis when including all stages. However, in the clinically most interesting prognostic group, Dukes' stage B patients, high nuclear accumulation of β-catenin was associated with a poor prognosis (p=0.01). Our results suggest that nuclear accumulation of β-catenin in CRC is related to CIN and may be of prognostic importance. However, larger studies are needed to verify these findings.