Kroneman Trynda N, Voss Jesse S, Lohse Christine M, Wu Tsung-Teh, Smyrk Thomas C, Zhang Lizhi
Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Endocr Pathol. 2015 Sep;26(3):255-62. doi: 10.1007/s12022-015-9379-2.
The Ki-67 index is essential in the pathological reports for pancreatic neuroendocrine tumors. There are three methods to determine the Ki-67 index including eyeball estimation, manual counting, or automated digital imaging analysis. The goal of this study was to compare the three quantification methods with the clinical outcome to determine the best method for clinical practice. Ki-67 immunostaining was performed on 97 resected pancreatic neuroendocrine tumors. The three methods of quantification were employed: (1) an average of eyeball estimation by three pathologists; (2) manual counting of at least 500 tumor cells; and (3) digital imaging analysis quantitation by selecting 8-10 hot spot regions. All tumors were graded according to the 2010 WHO grading system. The three quantification methods for the Ki-67 index had almost perfect agreement. The concordance between manual counting and digital imaging analysis and between manual counting and average eyeball estimation were 0.97 and 0.88, respectively. The concordance among the three pathologists' eyeball estimation was 0.86. All three methods correlated with patients' survival using the 2010 WHO grading system. Eyeball estimation scores were significantly less than those of the other two methods and tended to downgrade more tumors to grade 1, but they had higher predictive ability for survival and recurrence. The WHO system using the mitotic rate could also separate patients with different survival and even downgraded more tumors to grade 1. The results suggest the necessity of a consensus among pathologists for the method to determine the Ki-67 index and proper cutoff of the Ki-67 index for better clinical correlation.
Ki-67指数在胰腺神经内分泌肿瘤的病理报告中至关重要。有三种方法可确定Ki-67指数，包括目测估计、手动计数或自动数字成像分析。本研究的目的是将这三种量化方法与临床结果进行比较，以确定临床实践的最佳方法。对97例切除的胰腺神经内分泌肿瘤进行了Ki-67免疫染色。采用了三种量化方法：（1）由三位病理学家进行目测估计的平均值；（2）至少手动计数500个肿瘤细胞；（3）通过选择8-10个热点区域进行数字成像分析定量。所有肿瘤均根据2010年世界卫生组织分级系统进行分级。Ki-67指数的三种量化方法几乎完全一致。手动计数与数字成像分析之间以及手动计数与目测估计平均值之间的一致性分别为0.97和0.88。三位病理学家目测估计之间的一致性为0.86。使用2010年世界卫生组织分级系统，所有三种方法均与患者的生存率相关。目测估计分数明显低于其他两种方法，并且倾向于将更多肿瘤降级为1级，但它们对生存和复发具有更高的预测能力。使用有丝分裂率的世界卫生组织系统也可以区分具有不同生存率的患者，甚至将更多肿瘤降级为1级。结果表明，病理学家之间有必要就确定Ki-67指数的方法以及Ki-67指数的适当临界值达成共识，以实现更好的临床相关性。
