LC3B globular structures correlate with survival in esophageal adenocarcinoma.
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.
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College, Cork, Ireland.
Shereen
S
El-Mashed
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College, Cork, Ireland.
Tracey R
TR
O'Donovan
Department of Pathology, Royal College of Surgeons Ireland (RCSI), Beaumont Hospital, Dublin, Ireland.
Elaine W
EW
Kay
National Liver Institute, Menoufiya University, Shebin El Kom, Egypt.
Ayat R
AR
Abdallah
Department of Surgery & Trinity Centre for Health Sciences, St James Hospital, Dublin, Ireland.
Mary-Clare
MC
Cathcart
Department of Surgery & Trinity Centre for Health Sciences, St James Hospital, Dublin, Ireland.
Jacintha
J
O'Sullivan
Department of Pathology, Royal College of Surgeons Ireland (RCSI), Beaumont Hospital, Dublin, Ireland.
Anthony
A
O'Grady
Department of Surgery & Trinity Centre for Health Sciences, St James Hospital, Dublin, Ireland.
John
J
Reynolds
Department of Oncology, Cork University Hospital, Cork, Ireland.
Seamus
S
O'Reilly
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College, Cork, Ireland.
Gerald C
GC
O'Sullivan
Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College, Cork, Ireland. s.mckenna@ucc.ie.
Sharon L
SL
McKenna
D001343:Autophagy; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins