Correlation of elevated ALCAM shedding with patient outcome in colorectal cancer.

Abstract

46 Background: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is a cell-cell adhesion protein that has been highlighted as a putative biomarker for the progression of many cancers, including colorectal cancer (CRC). Current prognosis for CRC patients predominantly rely on pathologic staging classification. Although TNM staging successfully stratifies high-risk patients, there is significant variability in the rate of disease progression within each stage. Previous studies evaluating ALCAM as a biomarker for predicting colorectal cancer patient survival have published conflicting and inconclusive results. The aim of this present study was to investigate the prognostic value of ALCAM shedding, quantified using a dual stain that detects both the extracellular and the intracellular domains in formalin-fixed tissue, in colorectal patients. Methods: A novel dual-immunohistological detection of ALCAM shedding was performed on tissue microarrays constructed from 75 colorectal primary tumors and 9 healthy control specimens. Tissue was assessed by CellProfiler image analysis to obtain quantitative estimates of ALCAM shedding, defined as the detection of the intracellular domain the absence of the extracellular domain of ALCAM. Two tailed p values ≤ 0.05 were considered to be statistically significant. Results: ALCAM shedding was elevated in 33/79 (41.8%) of tissue from CRC patients compared to healthy controls (p=0.0239). Univariate analysis of CRC patients, stages I-IV, revealed a statistical significance correlating high ALCAM shedding with worse overall survival (p=0.0401). Moreover, ALCAM shedding is a predictor of overall survival (p=0.432) and more notably, disease-specific survival in stage II patients (p=0.0098). Conclusions: Detection of ALCAM shedding allows for stratification of patients according to their risk for poor long-term outcome. Considering that ALCAM is altered in a number of malignancies, the clinical correlation of ALCAM shedding to patient outcome is likely to extend beyond CRC to other cancers.