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Fareed, Khaleel R. and Soomro, Irshad N. and Hameed, Khalid and Arora, Arvind and Lobo, Dileep N. and Parsons, Simon L. and Madhusudan, Srinivasan (2012) Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy. World Journal of Gastroenterology, 18 (16). pp. 1915-1920. ISSN 1007-9327

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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.

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