Wakizaka Kazuki, Yokoo Hideki, Kamiyama Toshiya, Kakisaka Tatsuhiko, Ohira Masafumi, Tani Michio, Kato Koichi, Fujii Yuki, Sugiyama Ko, Nagatsu Akihisa, Shimada Shingo, Orimo Tatsuya, Kamachi Hirofumi, Matsuoka Ryosuke, Taketomi Akinobu
Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Pathology, International University of Health and Welfare, Mita Hospital, Tokyo, Japan.
Hepatol Res. 2020 Feb;50(2):258-267. doi: 10.1111/hepr.13443. Epub 2019 Dec 18.
A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification.
We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis.
Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA.
INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.
最近报道了一种新的肝细胞胆管癌（CHC）分类方法。癌症干细胞与CHC的致癌作用有关。本研究探讨了使用新分类法分类的CHC中癌症干细胞标志物表达与预后的关系。
我们纳入了26例CHC患者，并根据新分类法对其进行分类。我们通过免疫组织化学染色评估了每个成分中癌症干细胞标志物（CD56、CD133和上皮细胞粘附分子[EpCAM]）的表达。我们分析了表达与预后之间的关联。
7例为肝细胞癌（HCC）和胆管癌（CCA）（cHCC-CCA），12例为HCC和中间细胞癌（HCC-INT），7例为中间细胞癌（INT）。在cHCC-CCA中，CCA（42.9%）和INT成分（50.0%）的CD133阳性率倾向于高于HCC成分（14.3%）。在HCC-INT中，INT成分（83.3%）的CD133阳性率显著高于HCC成分（8.3%；P = 0.001）。对于EpCAM，在cHCC-CCA中，CCA成分（71.4%）和INT成分（50.0%） 的阳性率倾向于高于HCC成分（14.3%）。在cHCC-CCA中，CD133阳性（分别为P = 0.048和P = 0.048）或EpCAM阳性（分别为P = 0.041和P = 0.041）的CCA成分患者的总生存期和无病生存期明显更差。
INT和CCA成分显示出比HCC成分更高的癌症干细胞标志物表达率。cHCC-CCA中CCA成分的CD133或EpCAM表达与预后不良有关。
