Clinicopathological significance of fibrotic capsule formation around liver metastasis from colorectal cancer

Abstract

Purpose: The fibrous capsule around hepatocellular carcinoma is well known to be an indicator of a good prognosis. However, the fibrotic stromal response in the liver to a metastatic tumor remains unclear. Patients and methods: In order to clarify the prevalence of fibrotic capsular formation around liver metastases as well as the prognostic and biological significance of the fibrotic capsule, 69 colorectal cancer patients, who underwent radical hepatectomy due to liver metastases, were investigated using immunohistochemical methods. Results: Encapsulated metastases as defined by a thick fibrotic band surrounding the entire surface of a metastasis were detected in 20% of the cases. The rate of initial recurrence in the remnant liver, which is a strong indicator for poor prognosis of colorectal liver metastasis, was significantly lower in the encapsulated metastasis group as compared with the non-encapsulated metastasis group. Proliferating fibroblastic cells in the capsule were myofibroblasts positively stained for α-smooth muscle actin (α-SMA) and they deposited dense extracellular matrices rich in collagen Type 1 in the layer of the inner half and secreted MMP-1, MMP-2, and TIMP-1 in the layer of the outer half of the capsule. Activation of α-SMA positive hepatic stellate cells (HSC) was also observed in the liver parenchyma adjacent to metastases. Conclusions: The results indicate that fibrotic capsular formation is associated with a lower rate of initial local recurrence in the remnant liver, and that the capsule may serve as a mechanical and chemical barrier to local invasion by metastatic tumor cells. Proliferating stromal cells in the capsule are myofibroblasts, probably derived from HSC activated by colorectal liver metastasis in the liver parenchyma.