Komatsubara Toshihide, Oshiro Hisashi, Sakuma Yasunaru, Sata Naohiro, Niki Toshiro, Fukushima Noriyoshi
Department of Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, Japan, 329-0498.
Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, Japan, 329-0498.
Pathol Int. 2019 Feb;69(2):86-93. doi: 10.1111/pin.12769. Epub 2019 Feb 6.
Bile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.
已知胆管癌含有大量成纤维细胞，且有报道称其通过分泌血小板衍生生长因子-D（PDGF-D）来招募癌症相关成纤维细胞，而PDGF-D需要丝氨酸蛋白酶（如matriptase）作为配体才能发挥作用。然而，它们的表达模式和预后价值尚未明确。在本研究中，我们调查了肝外胆管癌患者中PDGF-D和matriptase表达的临床病理意义。样本取自1991年至2015年间接受手术切除的256例患者，通过免疫组织化学评估PDGF-D和matriptase的表达水平。对染色强度和分布进行评分，最终分别将癌细胞和基质中的表达分为低表达组和高表达组。在91个肿瘤（40%）中检测到癌基质中matriptase高表达。癌基质中matriptase高表达与无复发生存期（RFS）和总生存期（OS）显著缩短相关（分别为P = 0.0027和0.0023）。多因素分析还表明，基质中matriptase表达水平是RFS（P = 0.0050）和OS（P = 0.0093）的独立影响因素。我们的研究结果表明，癌基质中matriptase高表达与肝外胆管癌患者的肿瘤进展、复发及不良预后密切相关。
