OncoTargets and Therapy (Sep 2017)
Molecular classification of esophagogastric junction carcinoma correlated with prognosis
Abstract
Long Zou,1,2 Yinying Wu,1 Ke Ma,1 Yangwei Fan,1 Danfeng Dong,1 Ningyan Geng,2 Enxiao Li1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 2Department of Gastroenterology, Shangluo Central Hospital, Shangluo, Shaanxi, People’s Republic of China Abstract: A novel molecular classification of gastric cancer by the Asian Cancer Research Group (ACRG) is a potential advance in diagnosis and treatment, and it helps to determine prognosis. The use of immunohistochemistry (IHC) rather than gene expression analysis to determine tumor subtypes was evaluated with the aim of determining the feasibility of using the ACRG molecular classification. A total of 69 esophagogastric junction (EGJ) carcinomas were classified as microsatellite instable (MSI, 17.40%, 12 of 69), microsatellite stable with markers of epithelial-to-mesenchymal transition (MSS/EMT, 18.84%, 13 of 69), microsatellite stable with active tumor protein 53 (MSS/TP53+, 27.53%, 19 of 69), and microsatellite stable with inactive TP53 (MSS/TP53-, 36.23%, 25 of 69). The molecular classification did not significantly correlate with anyone of the clinicopathological characteristics of the EGJ carcinoma patients, including age, gender, depth of tumor invasion, the presence of lymph node metastasis, histologic grade, and p-TNM stage of the American Joint Committee on Cancer (P>0.05). Kaplan–Meier survival analysis and log rank tests showed that molecular classification, histologic grade, p-TNM stage, and postoperative adjuvant chemotherapy were significantly associated with overall survival (OS; P<0.05). MSI tumors had the best overall prognosis followed by MSS/TP53- and MSS/TP53+. MSS/EMT tumors had the worst overall prognosis. Multivariate analysis revealed that histologic grade (hazard ratio [HR] =2.216, 95% CI =1.202–4.086), p-TNM stage (HR =2.216, 95% CI =1.202–4.086), and molecular subtype (HR =2.216, 95% CI =1.202–4.086) were independently associated with OS. The preliminary results suggested that the ACRG molecular classification may be a valuable independent prognostic marker for EGJ carcinoma patients and could be performed by IHC analysis. Keywords: molecular biology, gastroesophageal junction, microsatellite instable, MDM2, immunohistochemical staining, survival
