Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan; Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan.
Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan.
Hum Pathol. 2018 Jun;76:28-36. doi: 10.1016/j.humpath.2018.02.010. Epub 2018 Feb 13.
We have previously reported that DJ-1 protein is up-regulated in cholangiocarcinoma compared with non-neoplastic epithelium of the bile duct in a study using liquid-chromatography mass spectrometry-based proteomics. The aim of this study was to clarify whether DJ-1 expression offers a biomarker for patients with invasive extrahepatic cholangiocarcinoma (EHCC) who undergo surgical resection with curative intent. Positive immunohistochemical (IHC) staining of DJ-1 was significantly more frequent in the cytoplasm of 96 invasive EHCCs (n = 28, 29.2%) than in that of 66 non-neoplastic epithelial lesions adjacent to invasive EHCC (n = 7, 10.6%; P = .006). No significant difference in clinicopathological features was evident between invasive EHCC patients with negative (n = 68) and positive (n = 28) IHC staining. However, negative IHC staining for DJ-1 in cytoplasm was selected as an independent risk factor for adverse prognosis on multivariate analysis (P = .004, hazard ratio 2.13, 95% confidence interval 1.28-3.57). Serum levels of DJ-1 in 16 invasive EHCC patients with metastasis were compared with 12 invasive EHCC patients without metastasis. Serum levels of DJ-1 tended to be higher in 16 patients with metastasis (median, 40.9 ng/ml) than in 12 patients without (27.6 ng/ml, P = .137). In addition, patients with high serum levels (≥ 40 ng/ml) of DJ-1 tended to have metastasis more frequently than those without (P = .054, Fisher's exact test). We concluded that IHC staining pattern and serum level of DJ-1 in patients with invasive EHCC might be predictive of prognosis and metastasis, respectively.
我们之前的研究使用基于液相色谱-质谱的蛋白质组学发现,与胆管的非肿瘤上皮相比,DJ-1 蛋白在胆管癌中上调。本研究的目的是阐明 DJ-1 表达是否为具有根治性手术切除意向的侵袭性肝外胆管癌(EHCC)患者提供生物标志物。96 例侵袭性 EHCC(n=28,29.2%)的细胞质中 DJ-1 的阳性免疫组化(IHC)染色明显比 66 例侵袭性 EHCC 相邻的非肿瘤上皮病变(n=7,10.6%)更频繁(P=0.006)。IHC 染色阴性(n=68)和阳性(n=28)的侵袭性 EHCC 患者的临床病理特征无显著差异。然而,多变量分析显示 DJ-1 细胞质 IHC 染色阴性是不良预后的独立危险因素(P=0.004,风险比 2.13,95%置信区间 1.28-3.57)。比较了 16 例有转移的侵袭性 EHCC 患者和 12 例无转移的侵袭性 EHCC 患者的 DJ-1 血清水平。16 例转移患者的 DJ-1 血清水平(中位数,40.9ng/ml)高于 12 例无转移患者(27.6ng/ml,P=0.137)。此外,DJ-1 血清水平较高(≥40ng/ml)的患者比没有转移的患者更倾向于转移(P=0.054,Fisher 确切检验)。我们得出结论,IHC 染色模式和 DJ-1 血清水平可能分别预测侵袭性 EHCC 患者的预后和转移。