Evaluation of the preoperative neutrophil-to-lymphocyte ratio as a predictor of the micropapillary component of stage IA lung adenocarcinoma.

OBJECTIVE: To assess the ability of markers of inflammation to identify the solid or micropapillary components of stage IA lung adenocarcinoma and their effects on prognosis. METHODS: We performed a retrospective study of clinicopathologic data from 654 patients with stage IA lung adenocarcinoma collected between 2013 and 2019. Logistic regression analysis was used to identify independent predictors of these components, and we also evaluated the relationship between markers of inflammation and recurrence. RESULTS: Micropapillary-positive participants had high preoperative neutrophil-to-lymphocyte ratios. There were no significant differences in the levels of markers of systemic inflammation between the participants with or without a solid component. Multivariate analysis showed that preoperative neutrophil-to-lymphocyte ratio (odds ratio [OR] = 2.094; 95% confidence interval [CI], 1.668-2.628), tumor size (OR = 1.386; 95% CI, 1.044-1.842), and carcinoembryonic antigen concentration (OR = 1.067; 95% CI, 1.017-1.119) were independent predictors of a micropapillary component. There were no significant correlations between markers of systemic inflammation and the recurrence of stage IA lung adenocarcinoma. CONCLUSIONS: Preoperative neutrophil-to-lymphocyte ratio independently predicts a micropapillary component of stage IA lung adenocarcinoma. Therefore, the potential use of preoperative neutrophil-to-lymphocyte ratio in the optimization of surgical strategies for the treatment of stage IA lung adenocarcinoma should be further studied.

Impact of minimal solid and micropapillary components on invasive lung adenocarcinoma recurrence.

BACKGROUND: The specific impacts of solid and micropapillary components on prognosis in lung adenocarcinoma remain unclear. Herein, we elucidated their distinct contributions to lung adenocarcinoma recurrence. MATERIALS AND METHODS: Lung adenocarcinoma was classified into solid and micropapillary absent (S-M-); solid absent, micropapillary present (S-M+); micropapillary absent, solid present (S + M-); and solid and micropapillary present (S + M+). Cumulative incidence of recurrence (CIR) was calculated using competing risk analysis. RESULTS: Of 994 adenocarcinomas, 650 (65.4%) were classified as S-M-; 152 (15.3%), S-M+; 148 (14.9%), S + M-; and 44 (4.4%), S + M+. In total, 168 (16.9%) patients had recurrence; 16 (1.6%) died from other causes. S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P < 0.001, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- had significantly higher CIR than S-M+ (P = 0.002). These differences remained significant in multivariable analysis. In stage IA, S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P = 0.006, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- and S + M+ had significantly higher CIR than S-M+ (P = 0.005, P = 0.008, respectively). These differences remained significant in multivariable analysis. CIR was not significantly different between S + M- and S-M+ subgroups. CONCLUSIONS: The presence of solid or micropapillary component (≥1%) was an independent risk factor for CIR; patients with solid component alone had a higher CIR than those with micropapillary component alone. In IA lung adenocarcinoma, patients with both solid and micropapillary components had a higher CIR than those with micropapillary component alone; the proportion of solid or micropapillary component was not associated with CIR.

Cancer-associated fibroblasts, matrix metalloproteinase-9 and lymphatic vessel density are associated with progression from adenocarcinoma in situ to invasive adenocarcinoma of the lung.

The present study aimed to investigate the roles of cancer-associated fibroblasts (CAFs), matrix metalloproteinase-9 (MMP-9) and lymphatic vessel density (LVD) during the progression from adenocarcinoma in situ (AIS) to invasive lung adenocarcinoma (IAC). A total of 77 patients with stage 0-IA lung adenocarcinoma were enrolled. The expression levels of α-smooth muscle actin, MMP-9 and D2-40 were immunohistochemically analyzed. Survival analysis was performed using the Kaplan-Meier method. In the non-invasive component, the proportion of CAFs and the expression levels of MMP-9 increased from AIS to IAC; however, the LVD was not significantly different. CAFs were positively correlated with levels of MMP-9. The LVD had no significant correlation with CAFs and MMP-9. In the invasive component, CAFs, MMP-9 and LVD were significantly higher in IAC compared with in minimally invasive adenocarcinoma. CAFs, MMP-9 and LVD were all positively correlated with each other. The micropapillary subtype in IAC was associated with overall survival (OS). The LVD in IAC, but not MMP-9 and CAFs, was associated with OS. CAFs, MMP-9 and LVD were involved in the progression from AIS to IAC. CAFs exhibited a strong association with MMP-9 levels in the non-invasive and invasive components. The increase in the proportion of CAFs and the expression levels of MMP-9 may have been an early event before the adenocarcinoma became invasive. Once the adenocarcinoma was invasive, the LVD served an important role in tumor invasion and metastasis, and hence may be used as a prognostic marker of poor OS in stage IA IAC.