July 2011, Vol. 40 No. 7 319 Vascular Endothelial Growth Factor C as a Predictor of Early Recurrence and Poor Prognosis of Resected Stage I Non-small Cell Lung Cancer Shuo Chueh Chen, 1,2 MD, Chuen Ming Shih, 1 MD, PhD, Guan Chin Tseng, 3 MD, Wei Erh Cheng, 1 MD, Jean Chiou, 4 , Michael Hsiao, 5 PhD, Min Liang Kuo, 6 PhD, Jen Liang Su, 4,7 PhD, Chih Yi Chen, 8 MD Introduction Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide, with a 5-year survival of around 15%. 1 Approximately 20% of patients present with stage I disease (T1N0M0 or T2N0M0) and undergo potentially curative surgical resection. 2 However, approximately 30% to 40% of patients with stage I NSCLC after completely resection relapse and ultimately die of recurrent disease. 3,4 Early postoperative recurrence, often defined as relapse within 36 months after surgery, occur with high variety in resected stage I disease. 5 Although adjuvant chemotherapy clearly improves disease-free survival in Stage IB patients, an absolute overall survival benefit has Abstract Introduction: Stage I non-small cell lung cancer (NSCLC) is potentially curable after completely resection, but early recurrence may influence prognosis. This study hypothesises that vascular endothelial growth factor C (VEGF-C) plays a key role in predicting early recurrence and poor survival of patients with stage I NSCLC. Materials and Methods: The expression of VEGF-C was immuno-histochemically (IHC) analysed in tumour samples of primary stage I NSCLC and correlated to early recurrence (< 36 months), disease-free survival, and overall survival in all 49 patients. Results: Early recurrence was identified in 16 patients (33%), and the early recurrence rate in strong and weak VEGF-C activity was significantly different (P = 0.016). VEGF-C was also an independent risk factor in predicting early recurrence (HR = 3.98, P = 0.02). Patients with strong VEGF-C staining also had poor 3-year disease-free survival (P = 0.008) and overall survival (P = 0.007). Conclusion: Strong VEGF-C IHC staining could be a biomarker for predicting early recurrence and poor prognosis of resected stage I NSCLC, if the results of the present study are confirmed in a larger study. A more aggressive adjuvant therapy should be used in this group of patients. Ann Acad Med Singapore 2011;40:319-24 Key words: Early recurrence, Stage I NSCLC, Survival, VEGF-C 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 2 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan 3 Department of Pathology, China Medical University Hospital, Taichung, Taiwan 4 Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan 5 The Genomics Research Center, Academia Sinica, Taipei, Taiwan 6 Institute of Toxicology, College of Medicine and Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan 7 Department of Biotechnology, Asia University, Taichung, Taiwan 8 Division of Chest Surgery, Department of Surgery, China Medical University Hospital, Taichung, Taiwan Address for Correspondence: Dr Chih-Yi Chen, Division of Chest Surgery and Cancer Center Department of Surgery, China Medical University Hospital No. 2, Yuh-Der Road, Taichung, Taiwan. Email: mimian88@gmail.com not yet been conclusively established. 6,7 In addition, a percentage of Stage IA patients develop recurrent disease within a short period but are not routinely administered adjuvant therapy according to recent treatment guidelines. 3 Clinical or biological markers that are predictive of early recurrence in these patients must be identified. If such markers are available, stage I patients at high-risk of recurrence can be selected to receive adjuvant chemotherapy while those at very low-risk are spared the treatment toxicity. Vascular endothelial growth factor C (VEGF-C), a member of the VEGF family, is believed to be the main specific lymphangiogenic factor, which activates both VEGF-C in Predicting Early Recurrence and Survival of Stage I NSCLC—Shuo Chueh Chen et al Original Article