Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
Exp Mol Pathol. 2010 Aug;89(1):27-35. doi: 10.1016/j.yexmp.2010.05.005. Epub 2010 May 16.
Cancer stem cells (CSCs) are thought to be a critical subpopulation in tumor development, progression, metastasis and recurrence, and the identification of these cells is an initial step in understanding their role in oncogenesis and in seeking valuable markers for diagnosis or development of targeting therapeutics.
To identify CSCs in hepatocellular carcinoma (HCC) specimens and define their tissue specificity.
Immunohistochemical staining of CSC markers: CD44, CD90, CD133 and aldehyde dehydrogenase (ALDH) was performed in 25 HCC specimens, 4 hepatoblastomas, 8 peri-malignant tissues, and 19 cases of viral hepatitis.
The positivity of CD44 staining in HCC specimens was significantly lower than in viral hepatitis specimens. The positive rate of CD133 in HCC was similar to viral hepatitis specimens. CD133(+) cells were largely localized to ALDH-positive cells in HCC as revealed by confocal microscopy. In contrast, the co-expression of both markers was visualized within vessels or in the portal areas in viral hepatitis. Moreover, among 7 liver specimens adjacent to HCC tissue, 3-6 samples were positive for CD44, CD90, CD133 and ALDH, especially in dysplastic cells. One of 4 hepatoblastoma cases was positive for all these markers; whereas, the other three specimens were negative for all these CSC markers.
In HCC and dysplastic tissues, clusters of CD133(+)/ALDH(high) cells were identified. The use of cancer stem cell markers to screen tissues with chronic liver diseases provides limited guidance in the identification of malignant cells.
癌症干细胞(CSC)被认为是肿瘤发生、发展、转移和复发的关键亚群,这些细胞的鉴定是了解其在肿瘤发生中的作用以及寻找有价值的诊断或靶向治疗标志物的初始步骤。
鉴定肝癌(HCC)标本中的 CSC 并定义其组织特异性。
对 25 例 HCC 标本、4 例肝母细胞瘤、8 例癌旁组织和 19 例病毒性肝炎进行 CSC 标志物 CD44、CD90、CD133 和醛脱氢酶(ALDH)的免疫组织化学染色。
HCC 标本中 CD44 染色的阳性率明显低于病毒性肝炎标本。HCC 中 CD133 的阳性率与病毒性肝炎标本相似。共聚焦显微镜显示,CD133(+)细胞主要定位于 HCC 中的 ALDH 阳性细胞。相比之下,在病毒性肝炎中,这两个标志物的共表达位于血管内或门脉区域。此外,在 7 例 HCC 组织旁的肝组织标本中,3-6 例标本对 CD44、CD90、CD133 和 ALDH 呈阳性,特别是在异型性细胞中。4 例肝母细胞瘤中有 1 例对所有这些标志物均呈阳性;而另外 3 例标本对所有这些 CSC 标志物均呈阴性。
在 HCC 和异型性组织中,鉴定出 CD133(+)/ALDH(高)细胞簇。使用癌症干细胞标志物筛选慢性肝病组织对鉴定恶性细胞的指导作用有限。