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

Clinicopathological significance of fibrotic capsule formation around liver metastasis from colorectal cancer
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DOI:
10.1007/s004320000199
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发表时间:
2001-03-01
影响因子:
3.6
通讯作者:
Yasui, K
Yasui, K
中科院分区:
医学3区
文献类型:
--
作者:
Lunevicius, R;Nakanishi, H;Yasui, K

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目的:众所周知,肝细胞癌周围的纤维包膜是预后良好的指标。然而,肝纤维化间质对转移性肿瘤的反应仍不清楚。患者和方法:为了阐明肝转移瘤周围纤维化包膜形成的发生率以及纤维化包膜的预后和生物学意义,采用免疫组化方法对69例因肝转移而接受根治性肝切除术的结直肠癌患者进行了研究。结果如下:20%的病例中检测到包裹性转移瘤,其定义为围绕转移瘤整个表面的厚纤维化带。与无包膜转移组相比,有包膜转移组的残肝首次复发率显著降低,残肝首次复发率是结直肠癌肝转移预后不良的一个强指标。囊内增殖的成纤维细胞是肌成纤维细胞,对x-平滑肌肌动蛋白(a-SMA)染色呈阳性,它们在内半层沉积富含1型胶原蛋白的致密细胞外基质,并分泌MMP-1、MMP-2和TIMP-1在囊的外半层。在转移灶附近的肝实质中也观察到α-SMA阳性肝星状细胞(HSC)的活化。结论:结果表明,纤维化包膜形成与残肝中较低的初始局部复发率相关,并且该包膜可作为转移性肿瘤细胞局部侵袭的机械和化学屏障。包膜中的增殖基质细胞是肌成纤维细胞,可能来源于肝实质中结直肠肝转移激活的HSC。
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 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 x-smooth muscle actin (a-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 alpha -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.