Stromal Expression of YKL-40 Correlates with Disease Free Survival in Colorectal Cancer.
Christopher N Chapman, Hannah Swayze, Michael Kuperman, Frida Rosenblum, Richard Arenas, Q Jackie Cao. Baystate Medical Center, Springfield, MA
Background: Advances in colorectal cancer (CRC) treatment has generated a need to discover predictive biomarkers. Increased serum levels of YKL-40, a secreted glycoprotein, has been inversely correlated with clinical outcome in many cancers, including CRC. To date, limited work has addressed if there is correlation between tissue expression of YKL-40 in CRC and clinical outcomes, such as disease free survival (DFS) and total survival (TS).
Design: Using clinical and tumor registry data we identified 281 patients with Stage 2-4 CRC with a minimum of 2-year follow-up. Immunohistochemistry was performed on archival tissue using a polyclonal YKL-40 antibody. Scores for percent of cells staining and staining intensity were combined for each specimen separately for epithelium and stroma to derive a total score which ranged from 0 to 6. Specimens with a total score ≥4 were classified as "positive (+)" and those <4 classified as "negative (-)". Cox regression was performed to assess the significance of stromal and epithelial expression in CRC in relationship to DFS and TS, controlling for stage and lymphatic invasion. Adjusted Hazard ratios indicate the risk of recurrence controlling for each variable.
Results: Fig 1 shows the crude DFS for patients according to total stromal score cutpoints (+/-). DFS for patient with "-" stromal score was superior to that for patient "+" score. Controlling for other variables in the Cox regression, "+" stromal score was an independent predictor of decreased DFS, (p<0.05). As expected, stage was also significantly related to DFS (p<0.001). Epithelial score and lymphatic invasion were not significant. Controlling for other variables, patients with "+" stromal scores were over twice as likely to recur (Hazard Ration = 2.1) as those with "-" scores. Stromal and epithelial scores showed no association with tumor stage. Tumor stage was the only predictor of TS by Cox regression.
Conclusions: Our results show a direct correlation between tumor specific stromal expression of YKL-40 and DFS in CRC. Lack of a significant association between stage and stromal score suggest that the latter is not merely a surrogate for the former. Our data suggests that stromal expression of YKL-40 predicts recurrence in CRC.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 56, Wednesday Morning