Esophageal adenocarcinoma, LC3B, Prognosis, Survival.
Egyptian Education Bureau, Higher Education Authority of Ireland, Breakthrough Cancer Research.
BACKGROUND: Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25 %. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict outcome. Previous studies have indicated that induction of autophagy can influence various aspects of tumor cell biology, including chemosensitivity. The objective of this study was to assess whether expression of the autophagy marker (LC3B) correlated with patient outcome.
METHODS: Esophageal adenocarcinoma tumor tissue from two independent sites, was examined retrospectively. Tumors from 104 neoadjuvant naïve patients and 48 patients post neoadjuvant therapy were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess impact of LC3B expression on survival. Cox regression was used to examine association with clinical risk factors.
RESULTS: A distinct globular pattern of LC3B expression was found to be predictive of outcome in both patient groups, irrespective of treatment (p < 0.001). Multivariate analysis found that this was a strong independent predictor of poor prognosis (p < 0.001).
CONCLUSIONS: This distinctive staining pattern of LC3B represents a novel prognostic marker for resectable esophageal adenocarcinoma.
Medical Pathology | Pathology
El-Mashed S, O'Donovan TR, Kay EW, Abdallah AR, Cathcart MC, O'Sullivan J, O'Grady A, Reynolds J, O'Reilly S, O'Sullivan GC, McKenna SL. LC3B globular structures correlate with survival in esophageal adenocarcinoma. BMC Cancer. 2015;15:582
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Clinical and histopathological data from both Group 1 (neoadjuvant-naïve) and Group 2 (neoadjuvant therapy) esophageal adenocarcinoma patients.
Additional file 2. Figure S1.tiff (2351 kB)
Evaluation of the autophagy marker LC3B in esophageal cancer cell lines following 5-fluorouracil (5-FU) treatment. Untreated and treated (40 μM 5-FU for 48 h) (A) OE21 and (B) KYSE450 cells were prepared as agrose cell pellets which were fixed, processed and stained by standard immunohistochemistry. Mild staining of LC3B is detected before and after treatment in OE21 cells, while in KYSE450 cells, staining is mild in pre-treatment sections, with strong staining observed following treatment (magnification 100×). Untreated and treated (40 μM 5-FU for 48 h) (C) OE21 and (D) KYSE450 cells were fixed and stained for LC3B. Immunofluorescence analysis of OE21 cells shows little if any staining with anti-LC3B, either pre- or post-treatment. In contrast, a small number of KYSE450 cells display LC3B staining, prior to treatment, while the extent and intensity of LC3B staining is significantly increased post treatment (magnification 400×). (Cytospins were fixed in 4 % PFA for 20 min and washed with PBS. Permeabilization was carried out with 0.2 % Triton X prior to staining with anti-LC3B).