Drg1 Expression in 131 Colorectal Liver Metastases: Correlation with Clinical Variables and Patient Outcomes

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Abstract
Purpose: The differentiation-related gene-1 (Drg1) is a recently identified gene down-regulated in malignancy and a putative suppressor of colorectal cancer metastases. Its expression is associated with improved survival in patients with prostate or breast cancer. Drg1 expression is also associated with resistance to irinotecan therapy in preclinical colorectal cancer models. The clinical evaluation of Drg1 in colorectal cancer has been limited. We performed this study to evaluate the role of Drg1 in a large cohort of patients with metastatic colorectal cancer who were irinotecan naïve. Experimental Design: We examined Drg1 expression by immunohistochemistry in 131 patients with metastatic colorectal cancer enrolled in a clinical trial of adjuvant fluorouracil-based therapy from 1991 to 1995. We correlated expression of Drg1 to numerous clinical and tumor related variables and to patient outcomes, including a subset of patients who recurred and received irinotecan-based therapy. Results: Drg1 expression was identified in all metastatic tissue samples. There was a trend for unilobar metastases with high Drg1 expression (P = 0.07) and a suggestion of improved 2-year survival (82.4% versus 69.6%, P = 0.148). High Drg1 expression suggested irinotecan resistance (P = 0.07). Conclusions: In colorectal cancer, Drg1 expression may be associated with a less aggressive, indolent colorectal cancer. High Drg1 may also be associated with relative resistance to irinotecan. The role of Drg1 in malignancy continues to be defined.