CHK2 Immunohistochemical Expression in Colon Cancer and its Relation with Clinicopathological Features and Outcome in Metastatic Colon Cancer Patients

Abstract

Background: The DNA damage checkpoint pathway has been of interest to the field of cancer biology, since checkpoint defects result in the accumulation of altered genetic information, a central feature of carcinogenesis. Little is known about the role that CHK2 (checkpoint kinase 2) gene plays in colorectal cancer tumorigenesis. The purpose of this study was to evaluate CHK2 expression in metastatic colon cancer and correlate it with clinicopathological features and patient survival. Methods: Tissues of primary tumors were obtained from 58 patients with metastatic colon cancer. The tissue microarray immunohistochemistry was the technique used to evaluate CHK2 expression. Statistical analysis used was SPSS17; p-value was set at <0.050. The relationship between the CHK2 immunohistochemical expression and the patients’ clinical and pathological features as well as survival data was reported. Results: CHK2 expression was positive in 69% of the cases. CHK2 expression was associated with lymph node status (p=0.012) and survival (p=0.034). Negative CHK2 expression increased the chance of lymph node involvement (Odds ratio: 10.23, p=0.03). The global survival time of CHK2-negative patients was higher (72 versus 59 months); the same trend emerged for progression-free survival time (19 versus 13 months). The survival curves differed depending on CHK2 expression in patients with or without lymph node involvement; survival was lower in CHK2-positive. A larger number of deaths occurred in CHK2-positive. Multivariate regression analysis identified performance status ECOG (p=0.01), synchronous metastasis (p=0.037), tumor cell differentiation (p=0.029) and CHK2 expression (p=0.020) as independent factors for overall survival. Conclusions: This study demonstrated that positive CHK2 expression in colon cancer indicates aggressiveness and impacts negatively patient survival and outcome. On the other hand, a negative expression indicates dissemination to lymph nodes.