The prognostic significance of MCL1 copy number gain in esophageal squamous cell carcinoma

Background: MCL1 copy number variations have been reported to be associated with cancer prognosis in several cancers. However, the role of MCL1 gain has not yet been determined in esophageal squamous cell carcinomas (ESCC). Methods: Fluorescence in situ hybridization (FISH) for MCL1 was performed on 262 ESCC samples using tissue microarray (TMA). Results: The median age of ESCC patients was 62 years (range 37-83), with frequencies between women (16.4%) and men (83.6%). Of the 262 tumors, 77 tumors (29.4%) had high MCL1 gain. In the multivariate analysis, lymph node metastasis (HR: 3.236, P<0.001 for DFS; HR: 3.501, P<0.001 for OS) and clinical stage (HR: 3.388, P<0.001 for DFS; HR: 3.616, P<0.001 for OS) were identified as independent worse prognostic factors. Interestingly, among patients without lymph node metastasis or stage I-II patients, high MCL1 gain was associated with better DFS (P=0.009 or 0.046) and OS (P=0.014 or 0.069) after disease free survival time was more than or equal to 12 months. Reversely, among patients with lymph node metastasis or stage III-IVa patients, high MCL1 gain was associated with poorer DFS (P=0.007 or 0.021) and OS (P=0.029 or 0.068) after disease free survival time was more than or equal to 29 months. Conclusion: We observed that high MCL1 gain had bidirectional prognostic significance in ESCC patients with different lymph node status or clinical stage. These findings might provide the useful way of detailed risk stratification in patients with ESCC, and an insight into pathogenesis and mechanism of progression in ESCC.