RESEARCH Overexpression of Autophagy-Related 16-Like 1 in Patients with Oral Squamous Cell Carcinoma Jen-Yang Tang & Edward Hsi & Ya-Chun Huang & Nicholas Chung-Heng Hsu & Wen-Chi Yang & Hsueh-Wei Chang & Chee-Yin Chai & Pei-Yi Chu Received: 30 October 2013 /Accepted: 26 June 2014 # Arányi Lajos Foundation 2014 Abstract Dyregulation of autophagy has been reported in various human cancers including oral squamous cell carcinoma (OSCC). The objective of this study was to link expression of autophagy-related 16-like 1 (ATG16L1), a protein essential for autophagosome formation, to clinical outcome in a cohort of 90 OSCC patients. Expression level of ATG16L1 was assessed by immunohistochemistry and an immunoreactivity score (IRS), ranging from 0 to 9, was assigned to each case. The results were correlated with clinicopathological parameters and outcome of patients. Twenty-seven patients (30 %) exhibited ATG16L1 overexpression as indicated by an IRS of 9. Overexpression of ATG16L1 was significantly associated with disease stage (p =0.001), size (p =0.031) of the tumor, lymph node metastasis (p =0.004), and histological grade (p =0.038). ATG16L1 over- expression significantly affected the overall survival (p =0.020) and time to recurrence (p =0.031) of OSCC patients in Kaplan- Meier analysis. The present study suggested that ATG16L1 may be used as a biomarker for selecting OSCC patients with a more aggressive phenotype. Keywords Autophagy . Oral cancer . Immunohistochemistry . Autophagy-related 16-like 1 Abbreviations OSCC Oral squamous cell carcinoma ATG16L1 Autophagy-related 16-like 1 IRS Immunoreactivity score ROC Receiver operating characteristics OS Overall survival TTR Time to recurrence Introduction Oral cancer is a major global public health problem. In 2008, it is estimated that 263,900 new cases and 128,000 deaths (from oral cancer) were reported worldwide [1]. Oral cancer also has one of the lowest 5-years survival rates of all major cancers, in large part due to the lack of effective treatment and failure to diagnose many lesions in the initial J.<Y. Tang Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan J.<Y. Tang Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan E. Hsi : N. C.<H. Hsu Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Y.<C. Huang : C.<Y. Chai (*) Department of Pathology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan e-mail: cychai@kmu.edu.tw W.<C. Yang Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan H.<W. Chang Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan C.<Y. Chai Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan P.<Y. Chu (*) Department of Pathology, St. Martin De Porres Hospital, No. 565, Sec. 2, Daya Road, Chiayi, Taiwan e-mail: chu.peiyi@msa.hinet.net P.<Y. Chu School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan Pathol. Oncol. Res. DOI 10.1007/s12253-014-9821-7