HER-2 expression has no adverse prognostic signficance in caucasian patients with gastro-oesophageal adenocarcinomas: Analysis of Brightfield double In Situ hybridisation (BDISH) for HER-2 gene amplification and immunohistochemistry for HER-2 protein expression


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Michelle Cunnell1, Alex Reecesmith2, Irshad Soomro3, Zia Chaudry3, Ian Ellis3, Simon Parsons2, Srinivasan Madhusudan1
1Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham University Hospitals, Nottingham, United Kingdom,2Department of Surgery, Nottingham University Hospitals, Nottingham, United Kingdom,3Department of Pathology, Nottingham University Hospitals, Nottingham, United Kingdom


Trastuzumab, a monoclonal antibody targeting HER2 has recently been shown to improve survival in combination with chemotherapy in a large multinational trial of HER2 positive asian and caucasian gastro-oesophageal (GOJ) adenocarcinomas. However the biological significance of HER2 expression in caucasian GOJ tumours remains controversial.


Formalin-fixed 245 human gastro-oesophageal tumours were constructed into tissue microarrays (TMA). The TMA consisted of 148 tumours (n=115 adenocarcinomas, n=33 SCC) not exposed to neoadjuvant chemotherapy and 97 tumours (n=78 adenocarcinoma, n=19 SCC) exposed to pre-operative platinum based chemotherapy. Gene amplification and protein expression of HER2 was investigated using BDISH and immunohistochemistry (IHC). A step-wise approach to IHC scoring was used similar to Targos Molecular Pathology, Germany. IHC 3+ or IHC 2+ / BDISH+ were considered HER2 positive.  Only adenocarcinomas were included in the analysis (n=193).


A total of 193 tumours were available for HER2 evaluation. 8/193 (9.3%) were HER2 positive. 75% of tumours that were IHC 3+ and 56% of tumours that were IHC 2+ were BDISH+. There was significant heterogeneity in tumours with regards to HER2 expression.  28% of HER2 positive tumours were poorly differentiated compared 60% in HER2 negative tumours (p=0.007). Although lower T stage (T1, T2) was more frequently seen in HER2 positive tumours compared to HER2 negative tumours this did not reach statistical significance (p=0.077). There were no other significant clinico-pathological correlations including patient survival. Sub-group analyses in primary surgery group and neoadjuvant chemotherapy group also showed no significant correlations.


Our data is in agreement with a recent IHC study of HER2 expression in gastric cancer by Grabsch et al.(1). The two studies (including ours) confirm that HER2 expression has no adverse prognostic significance in caucasian gastro-oesophageal adenocarcinomas.