Tumour regression grade (TRG) analyses in patients with resectable gastro-oesophageal adenocarcinomas treated with platinum-based neoadjuvant chemotherapy Khaleel R Fareed, Mohammad Ilyas, 1 Philip V Kaye, 1 Irshad N Soomro, 2 Dileep N Lobo, 3 Simon L Parsons, 4 and Srinivasan Madhusudan Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine & Health Sciences and 1 Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, 2 Department of Pathology, Nottingham University Hospitals, 3 Division of Gastrointestinal Surgery, Wolfson Digestive Diseases Centre, Queen’s Medical Centre, Nottingham University Hospitals and 4 Department of Surgery, Nottingham University Hospitals, Nottingham, UK Date of submission 16 September 2008 Accepted for publication 25 February 2009 Fareed K R, Ilyas M, Kaye P V, Soomro I N, Lobo D N, Parsons S L & Madhusudan S (2009) Histopathology 55, 399–406 Tumour regression grade (TRG) analyses in patients with resectable gastro-oesophageal adenocarcinomas treated with platinum-based neoadjuvant chemotherapy Aims: Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro- oesophageal adenocarcinoma. The aims were to vali- date the utility of the tumour regression grade (TRG) in patients who have received chemotherapy and to investigate if (i) TRG correlates with tumour down- staging and (ii) TRG could provide a comparative platform for future predictive biomarker investigations. Methods and results: Three pathologists were blinded to the treatment approaches. Review included diagnosis, tumour grade, TNM staging, vascular invasion, perineu- ral invasion, resection margin involvement and histo- pathological response to chemotherapy, as measured by TRG. In the neoadjuvant chemotherapy (CS) group (n = 84), 46.7% of gastric ⁄ gastro-oesophageal junction adenocarcinomas, and 45.5% of lower third oesopha- geal adenocarcinomas had TRG 1, 2 or 3 compared with 13.7% in the primary surgery group (n = 124) (P < 0.001and P = 0.006,respectively).IntheCSgroup, responders (TRG 1, 2 or 3) showed significant tumour downstaging [early ypT-stage disease (P = 0.002)]. In gastric cancers specifically, additional associations were seen with negative nodal disease (P = 0.044) and absence of vascular invasion (P = 0.027). Conclusions: TRG may reflect response to chemother- apy. In addition, positive correlations between TRG and ypTNM staging were demonstrated that would suggest tumour downstaging. Keywords: gastro-oesophageal cancers, neoadjuvant chemotherapy, tumour regression grade Abbreviations: 5-FU, fluorouracil; CF, cisplatin and 5-FU; CI, confidence interval; CS, chemosurgery; ECF, epirubicin, cisplatin and 5-FU; ECX, epirubicin, cisplatin and capecitabine; GOJ, gastro-oesophageal junction; HR, hazard ratio; MAGIC, Medical Research Council Adjuvant Gastric Infusional Chemotherapy; TRG, tumour regression grade Introduction Western countries have seen a significant recent increase in the incidence of distal oesophageal, gas- tro-oesophageal junction (GOJ) and proximal gastric adenocarcinoma. The overall prognosis for gastro- oesophageal tumours remains poor. 1–5 Although surgery plays a central role in the overall management of operable disease, 6–9 it is clear that additional therapy is required to improve patient outcomes. 10,11 The Address for correspondence: Dr S Madhusudan, Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, UK. e-mail: srinivasan.madhusudan@nottingham.ac.uk Ó 2009 The Authors. Journal compilation Ó 2009 Blackwell Publishing Limited. Histopathology 2009, 55, 399–406. DOI: 10.1111/j.1365-2559.2009.03404.x