Yoshizawa Takahiro, Uehara Takeshi, Iwaya Mai, Asaka Shiho, Nakajima Tomoyuki, Kinugawa Yasuhiro, Shimizu Akira, Kubota Koji, Notake Tsuyoshi, Masuo Hitoshi, Sakai Hiroki, Hosoda Kiyotaka, Hayashi Hikaru, Nagaya Tadanobu, Ota Hiroyoshi, Soejima Yuji
Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan; Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Pathology. 2023 Jun;55(4):508-513. doi: 10.1016/j.pathol.2022.11.007. Epub 2023 Feb 3.
IgG4-positive plasma cells are reportedly increased in the tumour microenvironment, and a high number of these cells in tumours is a poor prognostic factor in several cancers. However, there are no reported analyses of IgG4 expression in intrahepatic cholangiocarcinoma (ICC). This study aimed to analyse the correlations between prognosis-related clinicopathological features of patients with ICC and IgG4 expression. We identified 37 ICC patients who underwent surgical resection between January 2010 and December 2020. The number of IgG-positive and IgG4-positive plasma cells in the tumour, invasion front, and stroma near the tumour was analysed by immunostaining. Furthermore, we examined the association of prognosis-related clinicopathological data with the number of IgG4-positive plasma cells and IgG4/IgG ratio in ICC patients. The IgG4-positive plasma cell percentages for the intra-tumour area, invasion front, and non-cancerous area (NCA) near the tumour were 91.9%, 56.8%, and 81.1%, respectively. IgG-positive plasma cells were observed in each region for all cases, except for NCA tissue in one case. A high IgG4 expression level and IgG4/IgG ratio in the invasion front were significantly associated with poor overall survival (OS) (log-rank test p=0.0438 and p=0.0338, respectively). Multivariate analysis for OS revealed that high IgG4 expression (p=0.0140), lymph node metastasis (p=0.0205), and positive surgical margin (p=0.0009) or a high IgG4/IgG ratio (p=0.0051), lymph node metastasis (p=0.0280), and positive surgical margin (p=0.0009) were independent poor prognostic factors. In conclusion, a high IgG4 expression level and IgG4/IgG ratio in the invasion front are independent poor prognostic factors for ICC. Targeted therapy for IgG4 may improve the prognosis for patients with ICC.
据报道，肿瘤微环境中IgG4阳性浆细胞增多，肿瘤中大量的此类细胞在多种癌症中是预后不良的因素。然而，目前尚无关于肝内胆管癌（ICC）中IgG4表达的分析报道。本研究旨在分析ICC患者的预后相关临床病理特征与IgG4表达之间的相关性。我们纳入了2010年1月至2020年12月期间接受手术切除的37例ICC患者。通过免疫染色分析肿瘤、浸润前沿及肿瘤附近基质中IgG阳性和IgG4阳性浆细胞的数量。此外，我们还研究了ICC患者预后相关临床病理数据与IgG4阳性浆细胞数量及IgG4/IgG比值的关系。肿瘤内区域、浸润前沿及肿瘤附近非癌区域（NCA）的IgG4阳性浆细胞百分比分别为91.9%、56.8%和81.1%。除1例患者的NCA组织外，所有病例的各区域均观察到IgG阳性浆细胞。浸润前沿的高IgG4表达水平和IgG4/IgG比值与总生存期（OS）较差显著相关（对数秩检验p分别为0.0438和0.0338）。OS的多因素分析显示，高IgG4表达（p=0.0140）、淋巴结转移（p=0.0205）和手术切缘阳性（p=0.0009）或高IgG4/IgG比值（p=0.0051）、淋巴结转移（p=0.0280）和手术切缘阳性（p=0.0009）是独立的不良预后因素。总之，浸润前沿的高IgG4表达水平和IgG4/IgG比值是ICC的独立不良预后因素。针对IgG4的靶向治疗可能改善ICC患者的预后。
