TY - JOUR
T1 - Microenvironmental changes in the progression from adenocarcinoma in situ to minimally invasive adenocarcinoma and invasive lepidic predominant adenocarcinoma of the lung
AU - Naito, Masahito
AU - Aokage, Keiju
AU - Saruwatari, Kouichi
AU - Hisakane, Kakeru
AU - Miyoshi, Tomohiro
AU - Hishida, Tomoyuki
AU - Yoshida, Junji
AU - Masato, Sugano
AU - Kojima, Motohiro
AU - Kuwata, Takeshi
AU - Fujii, Satoshi
AU - Ochiai, Atsushi
AU - Sato, Yukitoshi
AU - Tsuboi, Masahiro
AU - Ishii, Genichiro
N1 - Funding Information:
This work was supported by the National Cancer Center Research and Development Fund ( 23-A-16 ) and JSPS KAKENHI ( 26108007 ).
Publisher Copyright:
© 2016 Elsevier Ireland Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Objectives Invasive lepidic predominant adenocarcinoma (LPA) of the lung is thought to progress in a stepwise fashion from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). The aim of this study was to investigate the microenvironmental changes during the development from AIS to LPA. Materials and methods Clinicopathological characteristics of AIS (n = 51), MIA (n = 59), LPA smaller than 3 cm (LPA-S, n = 113), and LPA larger than 3 cm (LPA-L, n = 47) were analyzed. We then evaluated the expression levels of epithelial-mesenchymal transition (EMT)-related molecules (E-cadherin, S100A4), invasion-related molecules (laminin-5, ezrin), stem-cell-related molecules (ALDH-1), and growth factor receptors (c-Met, 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 No significant difference in these characteristics was found between LPA-S and LPA-L. Laminin-5 expression in the non-invasive carcinoma component of MIA was significantly higher than that of AIS (p < 0.001). During the progression from MIA to LPA-S, the expression level of laminin-5 in the invasive carcinoma 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 carcinoma component of LPA-L was significantly increased (p < 0.05) compared to LPA-S; however, the number of tumor-promoting stromal cells were not different between these two groups. Conclusion Our current results indicated that microenvironmental molecular changes occur during the progression from MIA to LPA-S and suggested that this process may play an important role in disease progression from AIS to LPA.
AB - Objectives Invasive lepidic predominant adenocarcinoma (LPA) of the lung is thought to progress in a stepwise fashion from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). The aim of this study was to investigate the microenvironmental changes during the development from AIS to LPA. Materials and methods Clinicopathological characteristics of AIS (n = 51), MIA (n = 59), LPA smaller than 3 cm (LPA-S, n = 113), and LPA larger than 3 cm (LPA-L, n = 47) were analyzed. We then evaluated the expression levels of epithelial-mesenchymal transition (EMT)-related molecules (E-cadherin, S100A4), invasion-related molecules (laminin-5, ezrin), stem-cell-related molecules (ALDH-1), and growth factor receptors (c-Met, 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 No significant difference in these characteristics was found between LPA-S and LPA-L. Laminin-5 expression in the non-invasive carcinoma component of MIA was significantly higher than that of AIS (p < 0.001). During the progression from MIA to LPA-S, the expression level of laminin-5 in the invasive carcinoma 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 carcinoma component of LPA-L was significantly increased (p < 0.05) compared to LPA-S; however, the number of tumor-promoting stromal cells were not different between these two groups. Conclusion Our current results indicated that microenvironmental molecular changes occur during the progression from MIA to LPA-S and suggested that this process may play an important role in disease progression from AIS to LPA.
KW - Adenocarcinoma in situ
KW - Lepidic predominant lung adenocarcinoma
KW - Minimally invasive adenocarcinoma
KW - Stepwise progression
KW - Tumor microenvironment
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U2 - 10.1016/j.lungcan.2016.07.024
DO - 10.1016/j.lungcan.2016.07.024
M3 - Article
C2 - 27597281
AN - SCOPUS:84982797726
SN - 0169-5002
VL - 100
SP - 53
EP - 62
JO - Lung Cancer
JF - Lung Cancer
ER -
