Cyclin D1 expression predicts postoperative distant metastasis and survival in resectable esophageal squamous cell carcinoma

// Xue Hou 1 , Run-Bin Liang 2, 3 , Jin-Chang Wei 4 , Ying Xu 5 , Jian-Hua Fu 2, 3 , Rong-Zhen Luo 6 , Jie-Hua He 6 , Lan-Jun Zhang 2 , Peng Lin 2, 3 , Hao-Xian Yang 2, 3 1 Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou City, Guangdong Province, China 2 Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou City, Guangdong Province, China 3 Guangdong Esophageal Cancer Institute, Guangzhou City, Guangdong Province, China 4 Department of Thoracic Surgery, Linzhou Esophageal Cancer Hospital, Yaocun Town, Linzhou City, Henan Province, China 5 Institute of Medical Statistics and Epidemiology, Sun Yat-sen University Medical College, Guangzhou City, Guangdong Province, China 6 Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou City, Guangdong Province, China Correspondence to: Hao-Xian Yang, e-mail: yanghx@sysucc.org.cn Keywords: esophageal neoplasm, esophageal squamous cell carcinoma, cyclin D1, surgery, metastasis Received: February 13, 2016      Accepted: April 11, 2016      Published: April 28, 2016 ABSTRACT Purpose: We aim to identify esophageal squamous cell carcinoma patients with increased risk of postoperative metastases. Results: A high level of cyclin D1 expression, together with poor tumor cell differentiation and advanced tumor stages, increased risk of postoperative metastasis and decreased distant metastasis-free survival in ESCC in both cohorts. A high level of cyclin D1 expression also decreased overall survival in the training cohort ( p < 0.01) but not in the validation cohort ( p = 0.415). However, when the two cohorts of patients were pooled to obtain a larger case number, a high level of cyclin D1 expression was again demonstrated as an independent predictor that decreased overall survival ( p < 0.01). Methods: We used data from two institutions to establish training ( n = 319) and validation ( n = 164) cohorts. Tissue microarrays were generated for immunohistochemical evaluation. The correlation among cyclin D1 expression, clinicopathologic variables, postoperative distant metastases, overall survival, and distant metastasis-free survival were analyzed. Multivariate analyses were used to test the independent factors impacting postoperative distant metastases and survival. The outcomes generated from the training cohort were then tested using the validation cohort and pooled dataset. Conclusions: High level of cyclin D1 expression increased distant metastasis, decreased overall survival and distant metastasis-free survival in resectable ESCC. Using a combination of cyclin D1 expression, tumor cell differentiation grade, and tumor stages, identifying patients with increased risk of postoperative metastases becomes possible.