Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

Abstract

Amplification and overexpression of ErbB2 (Her2) is a frequent event in oesophageal adenocarcinomas. Assessment of ErbB2 status is crucial for identifying patients who are likely to benefit from treatment with trastuzumab. In this study, we performed a comprehensive analysis of ErbB2 amplification and expression in 142 oesophageal adenocarcinomas by comparing the most commonly used methods for ErbB2 assessment: ErbB2 expression was determined by immunohistochemistry and was scored (0, 1 þ , 2 þ and 3 þ ) according to a recently described modified scoring system for gastric cancer. ErbB2 amplification was evaluated by bright field double in situ hybridisation. The results were compared with pathologic features, patients' survival and previously published data from fluorescence in situ hybridisation analysis. On the basis of immunohistochemistry, which was applicable in 110 cores of the cases, 83 tumours (75%) had a score of 0 or 1 þ (immunohistochemistry negative), 13 tumours (12%) were scored as 2 þ and 14 tumours (13%) were scored as 3 þ . In situ hybridisation data were obtained from 142 cases. There was a highly significant correlation of immunohistochemistry, bright field in situ hybridisation and fluorescent in situ hybridisation (Po0.001 each). In total, 41 tumours (29%) were categorised as ErbB2 positive, which was defined as immunohistochemistry 3 þ and/or an ErbB2/Chr17 quotient of Z2 as assessed by either bright field double in situ hybridisation or fluorescence in situ hybridisation. ErbB2 positivity was observed more frequently in tumours with lower differentiation grades (P ¼ 0.029). Patients with ErbB2-positive tumours had a significantly worse prognosis, both in univariate analysis (P ¼ 0.004) and in multivariate analysis (P ¼ 0.03).In conclusion, we demonstrate that a significant number of oesophageal adenocarcinomas are positive for ErbB2. Assessment of ErbB2 amplification can be equivalently performed by conventional fluorescence in situ hybridisation or other lightmicroscopy-based methods, such as the novel bright field double in situ hybridisation technique. Modern Pathology (2011) 24, 908-916;

HER2 positivity in gastric and esophageal adenocarcinoma: clinicopathological analysis and comparison

“…In hindsight, a tendency toward higher HER2 positivity rate in proximal gastric tumors which are now classified as esophageal tumors is thus apparent in these studies. On the other hand, distal esophageal primary tumors (without growth in the GEJ) in our study showed 31.5 % HER2 positivity, which is higher than the 15-29 % HER2 positivity rate found in studies on distal esophageal adenocarcinoma alone (Yoon et al 2012a, b;Phillips et al 2012;Reichelt et al 2007;Langer et al 2011;Hu et al 2011). This could be related to underlying Barrett's esophagus in the primary distal esophageal tumors included in our study, which was frequently reported (25 of 54 distal esophageal tumors).…”

“…Similar HER2 positivity rates are reported in esophageal adenocarcinoma, though less extensively studied (Yoon et al 2012a, b;Phillips et al 2012;Reichelt et al 2007;Langer et al 2011;Hu et al 2011).…”

“…Overexpression of the HER2 oncogene, well known from its therapeutic impact in breast cancer, is described in 15-30 % of gastric and esophageal adenocarcinoma (Janjigian et al 2012;Tanner et al 2005;Gravalos and Jimeno 2008;Yoon et al 2012a, b;Phillips et al 2012;Bang et al 2009;Reichelt et al 2007;Langer et al 2011;Hu et al 2011). In our cohort of 321 patients, HER2 overexpression rate was 15.6 % with 50 patients showing HER2 positivity.…”

HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated adenocarcinoma: An Australian study

“…23,25 Some publications have suggested that HER2 overexpression is linked with poor prognosis in oesophageal cancer 26,27 while others have shown no relationship with prognosis. 28e30 Duhaylongsod et al 31 and Yoon et al 24 have stated that HER2 positive patients have better prognosis compared to HER2 negative patients, the latter study reporting that HER2 positivity was independently associated with improved overall survival with a HR ¼ 0.50 (95% CI: 0.33e0.78).…”

Genomics, Epigenetics and Molecular Considerations in Esophageal Adenocarcinoma: What You Need to Know?

“…The most common receptor mutations seen in early stages of EAC are activating missense mutations and inframe deletions of the Epidermal Growth Factor Receptor (EGFR) [5]. On the other hand, HER2 and c-MYC amplifications tend to develop in later stages of the disease and are associated with poor prognosis [6,7]. Interestingly, recent data seem to suggest that HER2 and EGFR are frequently amplified synchronously and preferentially dimerize with one another [8].…”