Fareed KR, Soomro IN, Hameed K, Arora A, Lobo DN, Parsons SL, Madhusudan S. Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy. World J Gastroenterol 2012; 18(16): 1915-1920 [PMID: 22563171 DOI: 10.3748/wjg.v18.i16.1915]
Corresponding Author of This Article
Dr. Srinivasan Madhusudan, FRCP, PhD, Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham University Hospitals, Nottingham NG5 1PB, United Kingdom. srinivasan.madhusudan@nottingham.ac.uk
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World J Gastroenterol. Apr 28, 2012; 18(16): 1915-1920 Published online Apr 28, 2012. doi: 10.3748/wjg.v18.i16.1915
Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy
Khaleel R Fareed, Irshad N Soomro, Khalid Hameed, Arvind Arora, Dileep N Lobo, Simon L Parsons, Srinivasan Madhusudan
Khaleel R Fareed, Khalid Hameed, Arvind Arora, Srinivasan Madhusudan, Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham University Hospitals, Nottingham NG5 1PB, United Kingdom
Irshad N Soomro, Department of Pathology, Nottingham University Hospitals, Nottingham NG5 1PB, United Kingdom
Dileep N Lobo, Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, Nottingham University Hospitals, Nottingham NG7 2UH, United Kingdom
Simon L Parsons, Department of Surgery, Nottingham University Hospitals, Nottingham NG5 1PB, United Kingdom
Author contributions: Fareed KR and Madhusudan S initiated the study, participated in its design and coordination, carried out the study, performed the statistical analysis and drafted the manuscript; Soomro IN conducted the histopathological analyses; Lobo DN and Parson SL were involved in the initiation of the study and manuscript preparation; Hameed K and Arora A were involved in manuscript preparation and correction; all authors approved the final version of the manuscript.
Correspondence to: Dr. Srinivasan Madhusudan, FRCP, PhD, Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham University Hospitals, Nottingham NG5 1PB, United Kingdom. srinivasan.madhusudan@nottingham.ac.uk
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Received: August 4, 2011 Revised: January 13, 2012 Accepted: February 8, 2012 Published online: April 28, 2012
Abstract
AIM: To examine cytokeratin-18 (CK-18) and caspase-cleaved CK-18 expression in tumours and correlate with clinicopathological outcomes including tumour regression grade (TRG) response.
METHODS: Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays. The first set consisted of 122 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 97 gastric/gastro-oesophageal cancer cases exposed to pre-operative platinum-based chemotherapy. Expression of CK-18 and caspase-cleaved CK-18 was investigated using immunohistochemistry.
RESULTS: CK18 was commonly expressed in gastro-oesophageal tumours (92.6%). Fifty-six point seven percent of tumours previously exposed to neoadjuvant chemotherapy were positive for caspase-cleaved CK-18 expression compared to only 24.6% of tumours not previously exposed to neoadjuvant chemotherapy (P = 0.009). In patients who received neoadjuvant chemotherapy, caspase-cleaved cytokeratin-18 expression correlated with favourable TRG response (TRG 1, 2 or 3, P = 0.043).
CONCLUSION: This is the largest study to date of CK-18 and caspase-cleaved CK-18 expression in gastro-oesophageal tumours. We provide the first evidence that caspase-cleaved CK-18 predicts tumour regression with neoadjuvant chemotherapy.
