LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer

Background: Most colorectal carcinomas are driven by an activation
of the canonical Wnt signalling pathway, which promotes the
expression of multiple target genes mediating proliferation
inavasion and invasion. Upon activation of the Wnt signalling
pathway its key player beta-catenin translocates from the cytoplasm
to the nucleus and binds to members of the T-cell factor
(TCF)/lymphoid enhancer factor (LEF-1) family namely LEF-1 and TCF4
which are central mediators of transcription. In this study we
investigated the expression of beta-Catenin, LEF1 and TCF4 in
colorectal carcinomas and their prognostic significance. Methods:
Immunohistochemical analyses of LEF-1, TCF4 and nuclear
beta-Catenin were done using a tissue microarray with 214
colorectal cancer specimens. The expression patterns were compared
with each other and the results were correlated with
clinicopathologic variables and overall survival in univariate and
multivariate analysis. Results: LEF-1 expression was found in 56
(26%) and TCF4 expression in 99 (46%) of colorectal carcinomas and
both were heterogenously distributed throughout the tumours.
Comparing LEF-1, TCF4 and b-catenin expression patterns we found no
correlation. In univariate analysis, TCF4 expression turned out to
be a negative prognostic factor being associated with shorter
overall survival (p = 0.020), whereas LEF-1 expression as well as a
LEF-1/TCF4 ratio were positive prognostic factors and correlated
with longer overall survival (p = 0.015 respectively p = 0.001). In
multivariate analysis, LEF-1 and TCF4 expression were confirmed to
be independent predictors of longer respectively shorter overall
survival, when considered together with tumour stage, gender and
age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4:
2.18; p = 0.014). Conclusions: This study demonstrates different
prognostic values of LEF-1 and TCF4 expression in colorectal cancer
patients indicating different regulation of these transcription
mediators during tumour progression. Moreover both factors may
serve as new potential predictive markers in low stage colon cancer
cases in advance.