Abstract
We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.
Highlights
Colorectal carcinoma is the fourth most common cancer in Western countries and the second leading cause of cancer-related deaths in Europe and North America [1, 2]
We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression
We determined that colorectal liver metastasis tissues exhibit significantly reduced osteoprotegerin expression compared to primary colorectal carcinomas and normal colorectal mucosa tissues
Summary
Colorectal carcinoma is the fourth most common cancer in Western countries and the second leading cause of cancer-related deaths in Europe and North America [1, 2]. In Korea, colorectal carcinoma is the third most common cancer, after thyroid carcinoma and stomach carcinoma, and is the fourth leading cause of cancerrelated deaths [3]. Despite major advances in surgical techniques and chemotherapeutic agents, the prognosis of colorectal carcinoma patients remains poor due to development of distant metastasis and recurrence [4]. Untreated colorectal liver metastasis has poor prognosis with a median survival of 6-12 months [4]. Evidence from numerous retrospective and comparative studies indicates that hepatic resection is the best potential curative treatment for colorectal liver metastasis that promotes long-term survival [6]. Hepatic resection for colorectal liver metastasis is associated with a 5-year survival rate of 25–51% [7]
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