Aberrant Wnt signaling is implicated in carcinogenesis triggering
efforts for the development of new therapeutic agents, many of which
have entered clinical trials. We extend our previous analysis of WNT3,
FZD7, LEFI expression levels in breast and colorectal cancer including
WNT2, FZD4 and beta-catenin expression, in an effort to delineate their
relative expression levels along with concurrent expression patterns and
possible prognostic value. We analyzed 82 breast and 102 colorectal
carcinomas for relative mRNA expression levels of the investigated genes
by RT-PCR relative quantification with the Delta Delta Ct method.
Statistical analysis was performed in order to determine associations of
relative mRNA expression and linear correlations. beta-catenin
expression was determined by immunochemistry. Regarding breast
carcinomas, decreased relative mRNA expression levels of WNT2, FZD4 were
found frequently and WNT2 expression was correlated with ER/ PR status
(p = 0.045/p = 0.028), whereas beta-catenin with grade (p = 0.026). In
colorectal carcinomas, increased relative mRNA expression levels of WNT2
and FZD4 were found in 59% and 32% of cases respectively, whereas
beta-catenin showed decreased mRNA expression levels in 57% of cases
and a correlation with pN-category (p = 0.037). Linear correlations were
observed between WNT2/FZD4 (R=0.542, p < 0.001), WNT2/beta-catenin
(R=0.254, p = 0.010), FZD4/beta-catenin (R=0.406, p < 0.001) expression
and a correlation between mRNA expression and membranous/cytoplasmic
beta-catenin emerged (p = 0.039/0.046). Our results suggest a possible
clinical significance for Wnt pathway gene expression levels in both
tumour types. The concurrent expression of the investigated genes as
well as the different expression profiles, underlines the complexity of
this pathway and the necessity of patient selection in order to maximize
the efficacy of drugs targeting Wnt pathway