Comprehensive analysis of spread through air spaces in lung adenocarcinoma and squamous cell carcinoma using the 8th edition AJCC/UICC staging system

Abstract

Background: This study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system. Methods: In total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically. Results: STAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis. Conclusions: Our findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.

Meta-Analysis of The Association Between Gene Mutation and Tumor Spread Through Air Space in Lung Adenocarcinoma

“…A total of 1047 articles were searched:9 from CBM, 158 from Embase, 251 from PubMed, 194 from Web of science,130 from Wanfang date, 32 from Veep and 273 from CNKI. After carefully inspection of these articles, 12 Original studies 7,[11][12][13][14][15][16][17][18][19][20][21] were nally enrolled in our meta-analysis. The detail processes of study selection were showed in the ow diagram (Fig.…”

“…A total of 11 original studies were included [11][12][13][14][15][16][17][18][19][20][21] . We combined these studies using random effects.…”

“…A total of 4 original studies were included 11,12,14,17 . We combined these studies using xed effects.…”

“…Metaanalysis results showed that BRAF mutation patients had a signi cantly increased incidence of STAS RR=2.12 95%CI 1.17~3.84 z=2.47 p=0.013 Fig. 4 2.2.4 The association between ALK genotype and STAS in lung adenocarcinoma A total of 7 original studies were included 7,11,12,[14][15][16]21 . We combined these studies using random effects.…”

Current status and perspectives of spread through air spaces in lung cancer

“…Furthermore, no significant difference was observed in the downregulation of E-cadherin, another EMT marker. However, Jia et al 27 reported that STAS was associated with low-E-cadherin expression, and high vimentin expression in adenocarcinoma and squamous cell carcinoma. Furthermore, Jin et al 52 reported that c-ros oncogene 1 (ROS1)-rearranged lung cancer showed frequent STAS-like aerogenous spread manifested by a decrease in Ecadherin levels; Lee et al 16 also reported that ROS-1 was highly expressed at 71% of STAS-positive tumors.…”