Assessment of relationships among clinicopathological characteristics, morphological computer tomography features, and tumor cell proliferation in stage I lung adenocarcinoma

Abstract

Background: Surgically resected stage I lung adenocarcinoma (ADC) has wide variation in prognosis. It is significant to identify high-risk patients and optimize therapeutic strategy. This study aimed to investigate the relationships among histological grade, serum tumor marker index (TMI), morphological computer tomography (CT) features, and a well-established prognosticator cell proliferation (Ki-67) in stage I ADC. Methods: Preoperative CT was performed in 182 patients with stage I ADC confirmed by pathology. The Ki-67 expression was acquired by immunohistochemistry. TMI was the square root of standardized serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) values. Tumor shadow disappearance rate (TDR) and other morphological CT features were interpreted by two radiologists. Histological grade, TMI, CT features were statistically evaluated to explore the associations with Ki-67 expression. Results: In univariate analysis, gender, smoking history, pack-year, histological grade, TNM stage (IA and IB), serum CEA and CYFRA 21-1 status, TMI status, as well as TDR, long-axis diameter, short-axis diameter, lobulation, spiculation, attenuation types, vacuolation, vascular invasion, vascular convergence, thickened bronchovascular bundles, pleural attachment and peripheral fibrosis were significantly associated with Ki-67 expression (all P<0.05). Solid-predominant ADC had the highest Ki-67 expression, followed by micropapillary, papillary and acinar-predominant ADC, while lepidic-predominant ADC had the lowest Ki-67 expression (P<0.001). TDR was negatively correlated with Ki-67 (r =-0.478, P<0.001). Multivariate logistic regression analysis revealed that gender, histological grade, TDR and attenuation types were independent factors associated with Ki-67 expression. Conclusions: Ki-67 expression differed distinctly according to ADC histological subtypes. High Ki-67 expression is independently associated with male patients of stage I ADC with worse differentiation, lower TDR and solid tumors, which might be of prognostic value for poor prognosis in stage I ADC.