Junichi Murakami1, Kazuhiro Ueda2, Fumiho Sano1, Masataro Hayashi1, Arata Nishimoto1, Kimikazu Hamano1. 1. Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan. 2. Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: kaueda@c-able.ne.jp.
Abstract
BACKGROUND: To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. METHODS: The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). RESULTS: Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). CONCLUSIONS: The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis.
BACKGROUND: To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. METHODS: The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). RESULTS: Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). CONCLUSIONS: The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis.
Authors: Jie Dai; Ming Liu; Stephen J Swensen; Shawn M Stoddard; Jason A Wampfler; Andrew H Limper; Gening Jiang; Ping Yang Journal: J Thorac Oncol Date: 2017-01-23 Impact factor: 15.609
Authors: Wassim W Labaki; Meng Xia; Susan Murray; Charles R Hatt; Abdullah Al-Abcha; Michael C Ferrera; Catherine A Meldrum; Lauren A Keith; Craig J Galbán; Douglas A Arenberg; Jeffrey L Curtis; Fernando J Martinez; Ella A Kazerooni; MeiLan K Han Journal: Chest Date: 2020-12-14 Impact factor: 9.410