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肝细胞、胆管细胞和肝癌干细胞标志物的免疫组织化学研究。

Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma.

机构信息

Department of Surgery, Teikyo University, School of Medicine, Tokyo, Japan.

出版信息

J Hepatobiliary Pancreat Sci. 2011 Jul;18(4):537-43. doi: 10.1007/s00534-010-0365-2.

DOI:10.1007/s00534-010-0365-2
PMID:21234612
Abstract

BACKGROUND/PURPOSE: Hepatocellular carcinomas (HCCs) commonly originate from pre-malignant lesions consisting of mature hepatocytes. However, recent studies have suggested that some HCCs emerge from hepatic stem/progenitor cells because stem/progenitor cell markers and cholangiocyte markers are found in these HCCs. At the same time, the expression of stem/progenitor cell markers and cholangiocyte markers may also indicate de-differentiation and transdifferentiation of ordinary HCC cells. This study was performed to help clarify the uncertainty surrounding these HCCs.

METHODS

Sixty-eight surgically resected HCC lesions no larger than 5 cm were studied immunohistochemically using a hepatocyte marker (Hepatocyte), 2 cholangiocyte markers (cytokeratins CK7 and CK19), a marker for mucin (Muc1), and a hepatic stem/progenitor cell marker (C-kit).

RESULTS

Hepatocyte, CK7, CK19, Muc1 and C-kit were positively stained in 68 cases (100%), 51 cases (75.0%), 15 cases (22.1%), 8 cases (11.8%) and 8 cases (11.8%), respectively. In those cases positive for CK7, CK19, Muc1 and C-kit, the positively stained cells formed small foci within a large area of negatively stained cells. Small-sized positive cells suggesting hepatic/stem cell origin were found rarely.

CONCLUSIONS

The positivity of cholangiocyte markers, the stem/progenitor cell marker and mucin production were thought to be due to transdifferentiation of HCC cells rather than malignant transformation of stem/progenitor cells.

摘要

背景/目的：肝细胞癌（HCC）通常起源于由成熟肝细胞组成的恶性前病变。然而，最近的研究表明，一些 HCC 来自于肝干细胞/祖细胞，因为这些 HCC 中存在干细胞/祖细胞标志物和胆管细胞标志物。同时，干细胞/祖细胞标志物和胆管细胞标志物的表达也可能表明普通 HCC 细胞的去分化和转分化。本研究旨在帮助澄清这些 HCC 中的不确定性。

方法

对 68 例大小不超过 5cm 的手术切除 HCC 病变进行免疫组织化学研究，使用肝细胞标志物（Hepatocyte）、2 种胆管细胞标志物（细胞角蛋白 CK7 和 CK19）、粘蛋白标志物（Muc1）和肝干细胞/祖细胞标志物（C-kit）。

结果

Hepatocyte、CK7、CK19、Muc1 和 C-kit 在 68 例（100%）、51 例（75.0%）、15 例（22.1%）、8 例（11.8%）和 8 例（11.8%）中呈阳性染色。在 CK7、CK19、Muc1 和 C-kit 阳性的病例中，阳性染色细胞在大片阴性染色细胞内形成小灶。很少发现提示肝/干细胞起源的小尺寸阳性细胞。

结论

胆管细胞标志物、干细胞/祖细胞标志物和粘蛋白产生的阳性被认为是 HCC 细胞的转分化，而不是干细胞/祖细胞的恶性转化。

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