Automated quantification of Ki-67 index associates with pathologic grade of pulmonary neuroendocrine tumors

作     者：Hai-Yue Wang Zhong-Wu Li Wei Sun Xin Yang Li-Xin Zhou Xiao-Zheng Huang Ling Jia Dong-Mei Lin 

作者机构：Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Pathology Peking University Cancer Hospital Institute Beijing 100142 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第5期

页      面：551-561页

核心收录：

学科分类：10[医学] 

主　　题：Antigen Ki-67 Computer-assisted numerical analysis Neuroendocrine tumor Prognostic factor 

摘      要：Background: Classification of the pulmonary neuroendocrine tumor (pNET) categories is a step-wise process identified by presence of necrosis and number of mitoses per 2 mm^2. In neuroendocrine tumor pathology, Ki-67 was first described as a prognostic factor in the pancreas and incorporated into the grading system of digestive tract neuroendocrine neoplasms in the 2010 WHO classification. However, the significance of Ki-67 in pNETs was still a controversial issue. This study was to investigate the potentially diagnostic value of Ki-67 in pNETs. Methods: We retrieved 159 surgical specimens of pNETs, including 35 typical carcinoids (TCs), 2 atypical carcinoid (ACs), 28 largecell neuroendocrine carcinomas (LCNECs), 94 small-cell lung cancers (SCLCs). Manual conventional method (MCM) and computer-assisted image analysis method (CIAM) were used to calculate the Ki-67 proliferative index. In CIAM, 6 equivalent fields lly annotated for digital image analysis. Results: The Ki-67 index among the 4 groups with ranges of 0.38% to 12.66% for TC, 4.34% to 29.48% for AC, 30.67% to 93.74% for LCNEC, and 40.71% to 96.87% for SCLC. The cutoff value of Ki-67 index to distinguish low grade with high grade was 30.07%. For the univariate survival analyses in pNETs, both the overall survival and progression-free survival correlated with Ki-67 index. In addition, the Ki-67 index performed by CIAM was proved to be of great positive correlation with MCM.(500 ×500 μm) at 10× magnification were manua Conclusions: Ki-67 index counted by CIAM is a reliable method and can be a useful adjunct to classify the low- and high-grade NETs.