Human epidermal growth factor receptor-2 in oesophageal cancers: an observational study

Abstract

Aim: To determine the incidence of human epidermal growth factor receptor 2 (HER2) over expression in oesophageal cancers.

Methods: A retrospective study, of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included. Cancer cases were diagnosed between April 2007 and June 2010. HER2 over expression was assessed using immunohistochemistry, those that scored "0" and "+1" were considered "negative" for HER2; those that scored "+3" were considered "Positive". Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colour in situ hybridisations (HER B DISH) assay and either came back to be positive or negative for HER2 over expression. Overall survival was measured from date of histological diagnosis until date of death. 93% of the cases were followed up till five years or death, and all were followed up till two years. Cases of gastro-oesophageal junctional tumours were excluded.

Results: The median age of our sample was 66 years (range: 38-91 years). Eighty one were male and 19 female. Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma. The anatomical distribution of the tumours was; upper oesophagus 2, middle oesophagus 11, and 87 were in the lower oesophagus. Operative resection was completed in 15 cases; seven cases had attempted surgical resections, i.e., open and close, 33 patients received definitive chemo-radiation and 52 had palliative treatment. Twenty-five of the cancers showed evidence of HER2 over expression, all were adenocarcinomas. Of the 25 cases that showed evidence of HER2 over expression, 21 (84%) were located in the lower third of the oesophagus. On staging, 24 out of the 25 HER2 positive cases were at stage 3 or more (13 at stage 3 and 11 at stage 4), For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4. Seventeen out of twenty five cases (68%) with HER2 over expression received palliative therapy, in comparison to thirty five out of seventy five (46.7%) in tumours not expressing HER2. No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not; median overall survival for HER2 positive tumours was 15 mo (95%CI, 11-19 mo) compared to 13 mo (95%CI, 9-17 mo) for HER2 negative ones. Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression (P = 0.576). Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis (P = 0.034 and P = 0.009 respectively). None of the patients included in this study received Trastuzumab.

Conclusion: Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression. Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.

Keywords: Dual-colour in situ hybridisations; Human epidermal growth factor receptor 2; Immunohistochemistry; Oesophageal adenocarcinoma; Trastuzumab.

Figure 1

Kaplan-Meier survival curves for human epidermal growth factor receptor 2 positive vs negative groups. HER2: Human epidermal growth factor receptor 2.