Abstract 5921: Microenvironmental changes in the progression from adenocarcinoma in situ to early-invasive adenocarcinoma of the lung

Abstract Introduction: Lepidic predominant adenocarcinoma of the lung was classified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (LPA) in current WHO classification, 4th edition. Furthermore, LPA is thought to progress in a stepwise fashion from AIS and MIA. However, those classifications were diagnosed by observation of pathologists based on morphology only. The aim of this study was to investigate the microenvironmental changes in the process of development from AIS, MIA to LPA, and subjective marker of stepwise progression. We have published a part of data in this study in Lung Cancer (100:53-62, 2016), and we believe that this study makes a contribution to elucidate the mechanism of development of LPA of the lung. Materials and Methods: Clinicopathological characteristics of AIS (n=51), MIA (n=59), LPA smaller than 3 cm (S-LPA, n=113), and LPA larger than 3 cm (L-LPA, n=47) were analyzed. We then immunohistochemically evaluated the expression levels of epithelial-mesenchymal transition (EMT)-related molecules (E-cadherin, S100A4), invasion-related molecules (laminin-5, ezrin), and growth factor receptors (EGFR) in cancer cells of each group (n=20). The number of tumor-promoting stromal cells, including podoplanin-positive cancer-associated fibroblasts (PDPN+ CAFs), CD204-positive tumor-associated macrophages (CD204+ TAMs), and CD34+ microvessel cells, were also analyzed. Results: LPA-S showed significantly frequent vascular and pleural invasion than MIA (p<0.05); however, no significant difference in those factors was found between S-LPA and L-LPA. Laminin-5 expression in the non-invasive component of MIA was significantly higher than that of AIS (p<0.001). During the progression from MIA to S-LPA, the expression level of laminin-5 in the invasive component was significantly elevated (p<0.01). Moreover, tumor-promoting stromal cells were more frequently recruited in the invasive area of LPA-S (PDPN+ CAFs; p<0.05, CD204+ TAMs; p<0.001, CD34+ microvessel; p<0.05). Ezrin expression in the invasive component of L-LPA was significantly increased (p<0.05) compared to S-LPA; however, the number of tumor- promoting stromal cells were not different between these two groups. Conclusion: Our current study indicated that microenvironmental molecular changes occur during the progression from MIA to S-LPA. Thus, it was suggested that this process may play an important role in disease progression from AIS to LPA of the lung. Citation Format: MASAHITO NAITO, Yukitoshi Satoh, Genichiro Ishii. Microenvironmental changes in the progression from adenocarcinoma in situ to early-invasive adenocarcinoma of the lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5921. doi:10.1158/1538-7445.AM2017-5921