Abstract：
BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) grading system predicts early lung adenocarcinoma outcomes.
METHODS: The purpose of this study is to examine prognostic value of the IASLC grading system and its association with the tumor microenvironment (TME) in Stage I EGFR-muted lung adenocarcinoma. Based on the IASLC grading system, we compared the clinicopathological characteristics of EGFR-mutated lung adenocarcinoma (n = 296). In addition, we examined the expression level of E-cadherin in tumor cells and counted the number of tumor-infiltrating lymphocytes (TILs; CD8, CD20, CD138, and Foxp3), tumor-associated macrophages (TAMs; CD204), and cancer-associated fibroblasts (CAFs; podoplanin) using semi-automatic digital pathology image analysis.
RESULTS: Recurrence-free survival (RFS) curve showed that survival of grade 3 was significantly shorter than that of grade 1 (P < 0.01) and grade 2 (P = 0.03). Multivariate analysis of RFS revealed the invasive size, lymphatic permeation, and grade 3 (P < 0.01) as independent poor prognostic factors. The number of CD204 +TAMs and PDPN+CAFs was significantly higher in grade 3 than in grade 1 or 2 (all P < 0.01). Among the intermediate grade by the predominant subtype based classification, cases classified as grade 3 by the new classification had higher number of CD204 +TAMs (P < 0.01) and PDPN+CAFs (P = 0.02) than those classified as grade 2.
CONCLUSIONS: The IASLC grading system correlated with the outcomes of EGFR-mutated lung adenocarcinoma. Grade 3 was found to have the TME that most contributes to tumor progression, which probably explained their poor prognosis.
METHODS: The purpose of this study is to examine prognostic value of the IASLC grading system and its association with the tumor microenvironment (TME) in Stage I EGFR-muted lung adenocarcinoma. Based on the IASLC grading system, we compared the clinicopathological characteristics of EGFR-mutated lung adenocarcinoma (n = 296). In addition, we examined the expression level of E-cadherin in tumor cells and counted the number of tumor-infiltrating lymphocytes (TILs; CD8, CD20, CD138, and Foxp3), tumor-associated macrophages (TAMs; CD204), and cancer-associated fibroblasts (CAFs; podoplanin) using semi-automatic digital pathology image analysis.
RESULTS: Recurrence-free survival (RFS) curve showed that survival of grade 3 was significantly shorter than that of grade 1 (P < 0.01) and grade 2 (P = 0.03). Multivariate analysis of RFS revealed the invasive size, lymphatic permeation, and grade 3 (P < 0.01) as independent poor prognostic factors. The number of CD204 +TAMs and PDPN+CAFs was significantly higher in grade 3 than in grade 1 or 2 (all P < 0.01). Among the intermediate grade by the predominant subtype based classification, cases classified as grade 3 by the new classification had higher number of CD204 +TAMs (P < 0.01) and PDPN+CAFs (P = 0.02) than those classified as grade 2.
CONCLUSIONS: The IASLC grading system correlated with the outcomes of EGFR-mutated lung adenocarcinoma. Grade 3 was found to have the TME that most contributes to tumor progression, which probably explained their poor prognosis.
摘要：
背景：国际肺癌研究协会（IASLC）分级系统可预测早期肺腺癌的预后。
方法：本研究的目的是检查IASLC分级系统的预后价值及其与I期EGFR减弱的肺腺癌中肿瘤微环境（TME）的相关性。基于IASLC分级系统，我们比较了EGFR突变肺腺癌的临床病理特征(n=296).此外,我们检测了E-cadherin在肿瘤细胞中的表达水平，并计数了肿瘤浸润淋巴细胞（TIL;CD8，CD20，CD138和Foxp3）的数量，肿瘤相关巨噬细胞（TAMs；CD204），和癌症相关的成纤维细胞（CAFs;podoplanin）使用半自动数字病理图像分析。
结果：无复发生存期（RFS）曲线显示，3级生存期明显短于1级（P<0.01）和2级（P=0.03）。RFS的多变量分析显示侵入性大小，淋巴渗透，3级（P<0.01）是独立的不良预后因素。3级CD204+TAMs和PDPN+CAFs的数量明显高于1级或2级（均P<0.01）。在中间等级中，按基于主要亚型的分类，新分类分类为3级的病例的CD204+TAM(P<0.01)和PDPN+CAF(P=0.02)数量高于2级.
结论：IASLC分级系统与EGFR突变肺腺癌的预后相关。发现3级具有对肿瘤进展最重要的TME，这可能解释了他们预后不佳的原因。
方法：本研究的目的是检查IASLC分级系统的预后价值及其与I期EGFR减弱的肺腺癌中肿瘤微环境（TME）的相关性。基于IASLC分级系统，我们比较了EGFR突变肺腺癌的临床病理特征(n=296).此外,我们检测了E-cadherin在肿瘤细胞中的表达水平，并计数了肿瘤浸润淋巴细胞（TIL;CD8，CD20，CD138和Foxp3）的数量，肿瘤相关巨噬细胞（TAMs；CD204），和癌症相关的成纤维细胞（CAFs;podoplanin）使用半自动数字病理图像分析。
结果：无复发生存期（RFS）曲线显示，3级生存期明显短于1级（P<0.01）和2级（P=0.03）。RFS的多变量分析显示侵入性大小，淋巴渗透，3级（P<0.01）是独立的不良预后因素。3级CD204+TAMs和PDPN+CAFs的数量明显高于1级或2级（均P<0.01）。在中间等级中，按基于主要亚型的分类，新分类分类为3级的病例的CD204+TAM(P<0.01)和PDPN+CAF(P=0.02)数量高于2级.
结论：IASLC分级系统与EGFR突变肺腺癌的预后相关。发现3级具有对肿瘤进展最重要的TME，这可能解释了他们预后不佳的原因。
