Evaluation and Prognostic Significance of Human Tissue Kallikrein-Related Peptidase 10 (KLK10) in Colorectal Cancer
William Dubinski, Constantina Petraki, Youssef Youssef, George M Yousef. St. Michael's Hospital, Toronto, ON, Canada; Metropolitan Hospital, Athens, Greece
Background: Conventional prognostic markers for colorectal cancer (CRC) rely on clinicopathological parameters and are not always accurate. Biomarkers contribute additional information that may increase prognostic accuracy. Members of the human kallikrein-related peptidases gene family represent potential CRC biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 10 (KLK10) by immunohistochemistry in CRC, and to correlate this expression with clinical outcome data.
Design: Clinico-pathologic data was collected for 62 cases of colorectal carcinoma. Each tumor was immunostained for KLK10 and a proportion score (PS) and an intensity score (IS) was calculated as follows: PS 0: none, 1: <1%, 2: 1-10%, 3: 11-30%, 4: 31-75%, 5: >75%. IS 0: none, 1: weak, 2: moderate, 3: strong. A total score (TS) with a range between 0 and 8 was obtained by the addition of PS and IS. We then compared our data with traditional clinicopathologic prognostic parameters and survival data.
Results: A statistically significant positive association was observed between KLK10 and tumor stage and liver metastases (p=0.015 and p=0.035, respectively). Paradoxically, a negative association was observed between KLK10 and tumor grade (p=0.009). Kaplan-Meier survival curves and univariate analysis showed that both KLK10 expression and stage had statistically significant correlations with disease-free survival (DFS) (p=0.030 and p<0.001, respectively) and overall survival (OS) (p=0.010 and p=0.001, respectively). Cox multivariate analysis showed that both KLK10 expression and stage were independent predictors of unfavorable DFS (p=0.057 and p=0.001, respectively) and OS (p=0.009 and p=0.001, respectively).
Conclusions: Our results show that increased KLK10 expression in CRC was associated with higher tumor stage, increased liver metastases, and decreased DFS and OS. Our data suggest that KLK10 might be used as an adjunct prognostic marker in CRC and implies that kallikreins play a prominent role in the pathogenesis of cancer.
Monday, March 19, 2012 1:00 PM
Poster Session II # 113, Monday Afternoon