Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy.

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.