Quaglia Alberto, McStay Mary, Stoeber Kai, Loddo Marco, Caplin Martyn, Fanshawe Thomas, Williams Gareth, Dhillon Amar
Department of Histopathology, Royal Free and University College Medical School, London, UK.
Liver Int. 2006 May;26(4):424-32. doi: 10.1111/j.1478-3231.2006.01242.x.
We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions.
Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN), and five dysplastic nodules (DN), identified in explant cirrhotic livers of five consecutive patients transplanted at Royal Free Hospital in 2002. Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of positive cells counted.
The proportion of cells expressing MCM2 was more than those expressing Ki67, which in turn was more than those expressing geminin (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a statistically significant trend of increasing Ki67 expression (P=0.006), from RN to HCC; this trend was not statistically significant for geminin (P=0.18) or MCM2 (P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four different cell kinetics patterns: 'resting' (G0 cells: MCM2 -ve, Ki67 -ve, geminin -ve); 'licensed' (MCM2 +ve, Ki67 -ve, geminin -ve); 'slowly growing' (G1 phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve, Ki67 +ve, geminin +ve) nodules.
The combination of MCM2, geminin and Ki67 could represent a valuable tool in the understanding of HCC progression in cirrhosis.
我们研究了肝硬化结节性病变的细胞周期动力学，以区分肝细胞癌（HCC）及其前驱病变。
2002年在皇家自由医院接受移植的连续5例患者的肝硬化外植肝中，识别出12个小肝癌、10个再生结节（RN）、6个大再生结节（LRN）和5个发育异常结节（DN）。进行了MCM2、geminin和Ki67的免疫过氧化物酶检测，并对阳性细胞的百分比进行计数。
表达MCM2的细胞比例高于表达Ki67的细胞，而表达Ki67的细胞又多于表达geminin的细胞（总体中位数分别为16%、2%和0.5%，P<0.001）。从RN到HCC，Ki67表达呈统计学显著增加趋势（P=0.006）；geminin（P=0.18）或MCM2（P=0.51）无统计学显著趋势。表达Ki67的细胞中位数百分比在RN中为1%，LRN中为0.5%，DN中为2.2%，HCC中为5.4%。这些标志物的组合确定了四种不同的细胞动力学模式：“静止”（G0期细胞：MCM2阴性、Ki67阴性、geminin阴性）；“许可”（MCM2阳性、Ki67阴性、geminin阴性）；“缓慢生长”（G1期阻滞，MCM2阳性、Ki67阳性、低（0.4%）geminin）和增殖（MCM2阳性、Ki67阳性、geminin阳性）结节。
MCM2、geminin和Ki67的组合可能是理解肝硬化中HCC进展的有价值工具。
