A Meta-Analysis of SMAD4 Immunohistochemistry as a Prognostic Marker in Colorectal Cancer.
OBJECTIVE
SMAD4 immunohistochemistry is considered a valuable prognostic marker in colorectal cancer, but individual studies have often been small and the results variable. A meta-analysis could potentially clarify these findings.


METHODS
In September 2014, a Pubmed and Google Scholar search was conducted to find publications that reported the prognostic value of SMAD4 expression. A meta-analysis was performed to clarify the association between SMAD4 expression and survival outcomes.


RESULTS
137 studies were found, of which 13 were considered eligible. The studies consisted of a total of 3800 patients. Three different endpoints were taken into account, namely, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In addition, the studies were divided into univariate and multivariate analyses. The pooled hazard ratios were given as follows: univariate CSS = 1.75 [95% confidence interval (CI): 0.93-3.32; z= 1.69; P= .09]; multivariate CSS = 2.17 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate DFS = 2.11 (95% CI: 1.36-3.28; z= 3.32; P= .001); multivariate DFS = 2.15 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate OS and DFS = 2.30 (95% CI: 1.41-3.73; z= 3.36; P= .001); univariate OS = 2.28 (95% CI: 1.30-4.00; z= 2.89; P= .004).


CONCLUSIONS
The results of the presented meta-analyses indicate that SMAD4 expression status using immunohistochemistry is a prognostic marker for patient survival.
Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: p.w.voorneveld@lumc.nl.
Philip W
PW
Voorneveld
Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands.
Rutger J
RJ
Jacobs
Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands.
Liudmila L
LL
Kodach
Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands.
James C H
JC
Hardwick