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

摘要

Background:Classification of the pulmonary neuroendocrine tumor (pNET) categories is a step-wise process identified by the presence of necrosis and number of mitoses per 2 mm2.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 (CLAM) were used to calculate the Ki-67 proliferative index.In CIAM,6 equivalent fields (500 × 500 μm) at 10× magnification were manually 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.Conclusions:Ki-67 index counted by CIAM is a reliable method and can be a useful adjunct to dassify the low-and high-grade NETs.