Toshida Katsuya, Itoh Shinji, Yugawa Kyohei, Kosai Yukiko, Tomino Takahiro, Yoshiya Shohei, Nagao Yoshihiro, Kayashima Hiroto, Harada Noboru, Kohashi Kenichi, Oda Yoshinao, Yoshizumi Tomoharu
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hepatol Res. 2023 May;53(5):432-439. doi: 10.1111/hepr.13875. Epub 2023 Jan 9.
The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs).
We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups.
We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.
成纤维细胞生长因子受体2（FGFR2）融合基因在肝内胆管癌（ICC）患者的FGFR通路中常作为一种基因异常被发现。由FGFR融合基因产生的FGFR融合蛋白被认为会导致肿瘤细胞生长。迄今为止，关于接受ICC肝切除术患者的病理FGFR2表达与预后之间的关系，以及FGFR2与肿瘤浸润淋巴细胞（TILs）之间的关系，报道较少。
我们纳入了92例行ICC肝切除术的患者，对FGFR2和分化簇8进行免疫组织化学染色，并对TILs进行苏木精-伊红染色以评估。分析FGFR2与临床病理特征及预后之间的关系，并将患者分为FGFR2阳性组（n = 18）和阴性组（n = 74）。FGFR2阳性组男性更多（p < 0.0001），血清白蛋白较低（p = 0.0355），癌胚抗原较高（p = 0.0099）。此外，多变量分析显示FGFR2阳性组无病生存期（DFS）较差（p = 0.0002）。多因素分析表明，DFS的独立预后因素为最大肿瘤直径（≥5 cm）（p = 0.0011）、肿瘤定位（肝门部类型）（p = 0.0180）和FGFR2阳性（p = 0.0029）。两组之间的TILs计数无显著差异。
我们表明FGFR2高表达是切除的ICC复发的独立预后因素。
