Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy

• Published in: British journal of cancer Vol. 102; no. 11; pp. 1600 - 1607
• Main Authors: Fareed, K R, Al-Attar, A, Soomro, I N, Kaye, P V, Patel, J, Lobo, D N, Parsons, S L, Madhusudan, S
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 25.05.2010
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Pharmacological - analysis; Biomarkers, Pharmacological - metabolism; Biomarkers, Tumor - metabolism; Cell Nucleus - metabolism; Cell Proliferation; Clinical outcomes; DNA-Binding Proteins - metabolism; Endonucleases - metabolism; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Platinum Compounds - administration & dosage; Prognosis; Stomach Neoplasms - diagnosis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Survival Analysis; Tissue Array Analysis; Translational Therapeutics; Treatment Outcome; Tumor Burden - physiology
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605686

Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro-oesophageal adenocarcinoma. Previously, we validated the utility of the tumour regression grade (TRG) as a histopathological marker of tumour downstaging in patients receiving platinum-based neoadjuvant chemotherapy. In this study we profiled key DNA repair and damage signalling factors and correlated them with clinicopathological outcomes, including TRG response. Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays (TMAs). The first set consisted of 142 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 103 gastric/gastro-oesophageal cancer cases exposed to preoperative platinum-based chemotherapy. Expressions of ERCC1, XPF, FANCD2, APE1 and p53 were investigated using immunohistochemistry. In patients who received neoadjuvant chemotherapy, favourable TRG response (TRG 1, 2 or 3) was associated with improvement in disease-specific survival (P=0.038). ERCC1 nuclear expression correlated with lack of histopathological response (TRG 4 or 5) to neoadjuvant chemotherapy (P=0.006) and was associated with poor disease-specific (P=0.020) and overall survival (P=0.040). We provide evidence that tumour regression and ERCC1 nuclear protein expression evaluated by immunohistochemistry are promising predictive markers in gastro-oesophageal cancer patients receiving neoadjuvant platinum-based chemotherapy.