Ko Gyung Hyuck, Go Se-Il, Lee Won Sup, Lee Jeong-Hee, Jeong Sang-Ho, Lee Young-Joon, Hong Soon Chan, Ha Woo Song
Department of Pathology Department of Internal Medicine Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
Medicine (Baltimore). 2017 Jun;96(25):e7181. doi: 10.1097/MD.0000000000007181.
Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic biomarker has not been established in gastric cancer. The present study was performed to investigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC).With tissue microarray for 320 patients with gastric cancer, we performed immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. For validation, we performed bootstrap resampling.The median follow-up duration was 72 months (range: 3-120 months). Ki-67-high group showed worse prognosis than Ki-67-low group in EGC (5-YSR, 78.9% vs 92.0%, P = .018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs 59.2%, P = .951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-high group was considerably worse than that for Ki-67-low group (5-YSR, 67.0% vs 94.4%, P = .012), but not in those with moderately differentiated (P = .504) and poorly differentiated histology (P = .905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r = 0.215, P = .002). Multivariate analysis also revealed that the high-Ki-67 expression serves as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397-13.515, P = .011), especially in the well-differentiated histology, but not in all the patients (P = .171). Bootstrap resampling internally validated this result (P = .011).This study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC with well-differentiated histologic type.
Ki-67蛋白是一种细胞增殖标志物。Ki-67作为预后生物标志物在胃癌中的作用尚未确立。本研究旨在探讨Ki-67表达作为早期胃癌（EGC）生物标志物的意义。我们对320例胃癌患者的组织芯片进行Ki-67免疫组化染色，并通过倾向评分匹配调整分析其临床意义。为进行验证，我们进行了自抽样重抽样。中位随访时间为72个月（范围：3 - 120个月）。在EGC中，Ki-67高表达组的预后比Ki-67低表达组差（5年生存率，78.9%对92.0%，P = 0.018），但在进展期胃癌（AGC）中并非如此（5年生存率，58.5%对59.2%，P = 0.951）。有趣的是，在高分化组织学的患者中，Ki-67高表达组的预后明显比Ki-67低表达组差（5年生存率，67.0%对94.4%，P = 0.012），但在中分化（P = 0.504）和低分化组织学的患者中并非如此（P = 0.905）。在该队列中，EGC比例与高分化组织学之间存在强相关性（r = 0.215，P = 0.002）。多因素分析还显示，高Ki-67表达是EGC的不良预后因素（HR 4.346，95%CI 1.397 - 13.515，P = 0.011），尤其是在高分化组织学中，但在所有患者中并非如此（P = 0.171）。自抽样重抽样内部验证了这一结果（P = 0.011）。本研究表明，Ki-67表达可能是高分化组织学类型EGC预后预测的良好生物标志物。
