Hayashi Akimasa, Misumi Kento, Shibahara Junji, Arita Junichi, Sakamoto Yoshihiro, Hasegawa Kiyoshi, Kokudo Norihiro, Fukayama Masashi
*Department of Pathology †Department of Surgery, Hepato-Biliary-Pancreatic Surgery Division, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Am J Surg Pathol. 2016 Aug;40(8):1021-30. doi: 10.1097/PAS.0000000000000670.
Previous studies have identified 2 clinically significant morphologic subtypes of intrahepatic cholangiocarcinoma (ICC) on the basis of anatomic location and/or histologic appearances. Recognizing that these classification schemes are not always applicable practically, this study aimed to establish a novel classification system based on mucin productivity and immunophenotype and to determine the rationale of this classification by examining the clinicopathologic and genetic characteristics of the 2 subtypes defined by this method. We retrospectively investigated 102 consecutive ICC cases and classified them on the basis of mucin productivity and immunophenotype (S100P, N-cadherin, and NCAM). We found that 42 and 56 cases were classified as type 1 and type 2 ICCs, respectively, and only 4 cases were of indeterminate type. Type 1 ICC, generally characterized by mucin production and diffuse immunoreactivity to S100P, arose less frequently in chronic liver diseases and showed higher levels of serum CEA and CA 19-9 than did type 2 ICC, which generally showed little mucin production and exhibited immunoreactivity to N-cadherin and/or NCAM. Type 1 ICC was characterized by several pathologic features, including higher frequencies of perineural invasion and lymph node metastasis. Although the log-rank test demonstrated that type 1 ICC had significantly worse survival, the multivariate Cox regression analysis showed no prognostic significance of this histologic subtype. Genetic analyses revealed that KRAS mutation was significantly more frequent in type 1 ICC, whereas IDH mutation and FGFR2 translocation were restricted to type 2 ICC. In conclusion, the present classification of ICC based on mucin productivity and immunophenotype identified 2 subtypes with clinicopathologic significance.
既往研究已根据解剖位置和/或组织学表现，确定了肝内胆管癌（ICC）的2种具有临床意义的形态学亚型。鉴于这些分类方案在实际应用中并不总是适用，本研究旨在建立一种基于黏蛋白产生和免疫表型的新分类系统，并通过检查用该方法定义的2个亚型的临床病理和基因特征来确定这种分类的基本原理。我们回顾性研究了102例连续的ICC病例，并根据黏蛋白产生和免疫表型（S100P、N-钙黏蛋白和NCAM）对其进行分类。我们发现，分别有42例和56例被分类为1型和2型ICC，只有4例为不确定型。1型ICC通常以黏蛋白产生和对S100P的弥漫性免疫反应为特征，在慢性肝病中出现的频率较低，并且与2型ICC相比，血清CEA和CA 19-9水平更高，2型ICC通常黏蛋白产生较少，并表现出对N-钙黏蛋白和/或NCAM的免疫反应。1型ICC具有多种病理特征，包括更高的神经周围侵犯和淋巴结转移频率。尽管对数秩检验表明1型ICC的生存率显著更差，但多变量Cox回归分析显示该组织学亚型无预后意义。基因分析显示，KRAS突变在1型ICC中显著更常见，而IDH突变和FGFR2易位仅限于2型ICC。总之，目前基于黏蛋白产生和免疫表型的ICC分类确定了2个具有临床病理意义的亚型。
