Ohno Akinobu, Yorita Kenji, Haruyama Yukihiro, Kondo Kazuhiro, Kato Atsuhiko, Ohtomo Toshihiko, Kawaguchi Makiko, Marutuska Kousuke, Chijiiwa Kazuo, Kataoka Hiroaki
Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Pathology Section, University of Miyazaki Hospital, Miyazaki, Japan.
Liver Int. 2014 Jul;34(6):942-52. doi: 10.1111/liv.12466. Epub 2014 Feb 7.
BACKGROUND & AIMS: The tumour cell microenvironment, which includes local oxygen saturation, pericellular pH and stromal cells, can modulate tumour progression. This study determined the prognostic impact of infiltrating tumour-associated macrophages and the expression of monocarboxylate transporter 4 (MCT4) and glypican 3 (GPC3) in hepatocellular carcinoma (HCC) clinical specimens.
A total of 225 cases of resected HCC were subjected to immunohistochemical analyses of CD68, CD204, MCT4 and GPC3. Immunoreactivities and other common clinicopathological parameters were subjected to univariate prognostic analyses for overall survival (OS, n = 225) and disease-free survival (DFS, n = 222). All variables with prognostic impact were further analysed in multivariate analysis.
Increased intratumoural infiltration of CD204-positive or MCT4-positive macrophages suggested shorter OS (P = 0.015 or P = 0.001 respectively), but DFS was not altered. The GPC3 score (with an emphasis on circumferential immunoreactivity) was correlated with shorter OS and DFS. Aberrant expression of MCT4 in HCC cells was observed in a subset of HCC cases (21%, 47/225). In those cases, significantly poorer OS (P < 0.0001) and DFS (P = 0.0003) were observed, and there was a positive correlation with the intratumoural infiltration of CD204- or MCT4-positive macrophages and the GPC3 score. Multivariate analysis showed that aberrant MCT4 expression in HCC cells was an independent prognostic factor for shorter OS (P = 0.018) and DFS (P = 0.006) after resection of HCC.
Aberrant expression of MCT4 in carcinoma cells serves as a novel, independent prognostic factor for HCC, indicating a poorer patient outcome.
肿瘤细胞微环境，包括局部氧饱和度、细胞周pH值和基质细胞，可调节肿瘤进展。本研究确定了浸润性肿瘤相关巨噬细胞以及单羧酸转运蛋白4（MCT4）和磷脂酰肌醇蛋白聚糖3（GPC3）在肝细胞癌（HCC）临床标本中的表达对预后的影响。
对225例手术切除的HCC病例进行CD68、CD204、MCT4和GPC3的免疫组织化学分析。对免疫反应性及其他常见临床病理参数进行总生存期（OS，n = 225）和无病生存期（DFS，n = 222）的单因素预后分析。对所有具有预后影响的变量进行多因素分析。
CD204阳性或MCT4阳性巨噬细胞的瘤内浸润增加提示OS缩短（分别为P = 0.015或P = 0.001），但DFS未改变。GPC3评分（强调周边免疫反应性）与较短的OS和DFS相关。在一部分HCC病例（21%，47/225）中观察到HCC细胞中MCT4的异常表达。在这些病例中，观察到OS（P < 0.0001）和DFS（P = 0.0003）明显较差，并且与CD204或MCT4阳性巨噬细胞的瘤内浸润以及GPC3评分呈正相关。多因素分析显示，HCC细胞中MCT4的异常表达是HCC切除术后OS缩短（P = 0.018）和DFS缩短（P = 0.006）的独立预后因素。
癌细胞中MCT4的异常表达是HCC的一种新的独立预后因素，表明患者预后较差。
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