Abstract
The aim of this study was to predict Ki-67 labeling index (LI) preoperatively by three-dimensional (3D) CT image parameters for pathologic assessment of GGO nodules. Diameter, total volume (TV), the maximum CT number (MAX), average CT number (AVG) and standard deviation of CT number within the whole GGO nodule (STD) were measured by 3D CT workstation. By detection of immunohistochemistry and Image Software Pro Plus 6.0, different Ki-67 LI were measured and statistically analyzed among preinvasive adenocarcinoma (PIA), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). Receiver operating characteristic (ROC) curve, Spearman correlation analysis and multiple linear regression analysis with cross-validation were performed to further research a quantitative correlation between Ki-67 labeling index and radiological parameters. Diameter, TV, MAX, AVG and STD increased along with PIA, MIA and IAC significantly and consecutively. In the multiple linear regression model by a stepwise way, we obtained an equation: prediction of Ki-67 LI=0.022*STD+0.001* TV+2.137 (R=0.595, R’s square=0.354, p<0.001), which can predict Ki-67 LI as a proliferative marker preoperatively. Diameter, TV, MAX, AVG and STD could discriminate pathologic categories of GGO nodules significantly. Ki-67 LI of early lung adenocarcinoma presenting GGO can be predicted by radiologic parameters based on 3D CT for differential diagnosis.
Highlights
Parameters of ground-glass opacity (GGO) were automatically calculated and displayed on the multi-display CT (MDCT) after 3D measurement by the CT lung analysis software. (Fig 4) The positive expression of Ki-67 presented tan particles located in nucleus of over proliferative cell
By Receiver operating characteristic (ROC) analysis, area under the curve (AUC) of diameter, total volume (TV), maximum CT number (MAX), average CT number (AVG), STD and Ki-67 labeling index (LI) is 0.801, 0.822, 0.890, 0.857, 0.901 and 0.907 respectively to differentiate preinvasive adenocarcinoma (PIA) from minimally invasive adenocarcinoma (MIA) and 0.812, 0.793, 0.749, 0.731, 0.684 and 0.901 respectively to rule out MIA from invasive adenocarcinoma (IAC). When it comes to the maximum true-positive ratio and the minimum false-positive ratio (1—specificity) simultaneously for parameters, we obtained the thresholds of all variables
As for quantitative and more accurate analysis, given GGO lesion was not homogeneous and no clear dividing line exists between pure GGO and mix GGO, we just regarded them as a continuous progression paralleling to pathological progression from AAH through AIS to MIA
Summary
Advances in high resolution CT (HRCT) scanning had increased the detection of ground-glass opacity (GGO) with data from many studies suggesting that localized GGO represents as a PLOS ONE | DOI:10.1371/journal.pone.0129206 June 10, 2015Ki-67 and Three-Dimensional Image Parameters in Ground-Glass Opacity precursor of lung adenocarcinoma.[1,2,3,4,5] Since a new international multidisciplinary classification of lung adenocarcinoma had been proposed by International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) in 2011, pathologic differentiation of GGO has been imperative and attractive for thoracic radiologists and surgeons.[6]GGO is a finding on HRCT lung images, and has been described as a hazy increase in lung attenuation without obscuring the underlying bronchial or vascular structures.[3, 7, 8] lesions without solid component in it were classified to pure GGO in comparison to mix GGO with solid component and ground glass attenuation in it as well. Advances in high resolution CT (HRCT) scanning had increased the detection of ground-glass opacity (GGO) with data from many studies suggesting that localized GGO represents as a PLOS ONE | DOI:10.1371/journal.pone.0129206. Ki-67 and Three-Dimensional Image Parameters in Ground-Glass Opacity precursor of lung adenocarcinoma.[1,2,3,4,5] Since a new international multidisciplinary classification of lung adenocarcinoma had been proposed by International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) in 2011, pathologic differentiation of GGO has been imperative and attractive for thoracic radiologists and surgeons.[6]. An awareness of the significance of CT attenuation number in assessing GGO has been reported recently.[12,13,14] Three-dimensional (3D) evaluation has been shown to be more sensitive and precise for quantifying small pulmonary nodules, for asymmetric nodules, than one- or two-dimensional methods.[15, 16]
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