Royal College of Surgeons in Ireland
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Apoptosis and autophagy markers predict survival in neoadjuvant treated oesophageal adenocarcinoma patients

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journal contribution
posted on 2022-10-28, 16:47 authored by Shereen El Mashed, Tracey R O'Donovan, Elaine KayElaine Kay, Anthony O'GradyAnthony O'Grady, Damian McManus, Richard C Turkington, Sharon L McKenna

Background: Less than 20 % of patients with resectable oesophageal adenocarcinoma obtain a pathological response following neoadjuvant chemotherapy. Studies using oesophageal cancer cell lines have shown that drug sensitive tumour cells undergo apoptosis in response to drug treatment, whereas resistant cells induce autophagy and can recover following withdrawal of drug. In this study, we evaluated markers of apoptosis (active/cleaved caspase-3) and autophagy (LC3B) to establish whether these markers are useful prognostic indicators following neoadjuvant therapy.

Methods: Oesophageal adenocarcinoma tumour tissue from the Northern Ireland Biobank at Queens University Belfast was examined retrospectively. Tumours from 144 patients treated with platinum-based neoadjuvant chemotherapy followed by surgical resection were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess the impact of cleaved caspase-3 and LC3B expression on survival. Cox regression was used to examine association with clinical risk factors.

Results: High levels of cleaved caspase-3 were found in 14.6 % of patients and this correlated with a significantly better overall survival (p = 0.03). 38.9 % of patients had high cytoplasmic LC3B expression, which correlated with poor overall survival (p = 0.041). In addition, a distinct globular pattern of LC3B expression was identified in 40.3 % of patients and was also predictive of overall survival (p < 0.001). LC3B globular structures are also associated with tumour recurrence (p = 0.014). When these markers were assessed in combination, it was found that patients who showed low/negative cleaved caspase-3 staining and high/positive staining for both patterns of LC3B had the worst overall survival (p < 0.001). Multi-variate analysis also indicated that this marker combination was an independent predictor of poor prognosis (p = 0.008; HR = 0.046, 95% CI = (0.005-0.443).

Conclusions: The expression of cleaved caspase-3 and specific LC3B staining patterns are associated with overall survival following neoadjuvant treatment. The combination of these markers is an independent indicator of outcome in neoadjuvant chemotherapy treated oesophageal adenocarcinoma.


Egyptian Education Bureau and Breakthrough Cancer Research

HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CR- UK Centre

Northern Ireland Experimental Cancer Medicine Centre

Friends of the Cancer Centre

Cancer Research UK, the Friends of the Cancer Centre and the Sean Crummey Foundation



The original article is available at

Published Citation

El Mashed S. et al. Apoptosis and autophagy markers predict survival in neoadjuvant treated oesophageal adenocarcinoma patients. BMC Cancer. 2022;22(1):908.

Publication Date

20 August 2022

PubMed ID



  • Beaumont Hospital
  • Pathology


BioMed Central


  • Published Version (Version of Record)