Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma

// Eunhyang Park 1 , Soo Young Park 2 , Ping-Li Sun 2, 6 , Yan Jin 2, 7 , Ji Eun Kim 3 , Sanghoon Jheon 4 , Kwhanmien Kim 4 , Choon Taek Lee 5 , Hyojin Kim 2, * , Jin-Haeng Chung 2, * 1 Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea 2 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 3 Department of Pathology, Seoul National University Boramae Hospital, Seoul, Republic of Korea 4 Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 5 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 6 Department of Pathology, Jilin University Second Hospital, Changchun, China 7 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China * These authors have contributed equally to this work Correspondence to: Hyojin Kim, email: hyojinkim7137@gmail.com Jin-Haeng Chung, email: chungjh@snu.ac.kr Keywords: cancer stem cell marker, immunohistochemistry, lung cancer, adenocarcinoma, Nanog Received: January 26, 2016      Accepted: May 16, 2016      Published: June 07, 2016 ABSTRACT Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma ( n = 226) or squamous cell carcinoma ( n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma.