HER‐2 overexpression/amplification in Barrett’s oesophagus predicts early transition from dysplasia to adenocarcinoma: a clinico‐pathologic study

Abstract

Barrett’s oesophagus (BO) is the primary precursor lesion for oesophageal adenocarcinoma (ADC). The natural history of metaplasia-dysplasia-carcinoma sequence remains largely unknown. HER2/neu oncogene results overexpressed/amplified in preneoplastic lesions and in ADC of the oesophagus and it has been associated with poor prognosis. Our aim was to evaluate the role of HER2 overexpression/amplification in predicting the conversion from precursor lesions to ADC. We retrospectively evaluated by univariate analysis of single variables clinical records and histological specimens of 21 patients with a confirmed diagnosis of BO and/or oesophageal dysplasia. Clinical variables included age, gender, alcohol and smoking intake, presence of symptoms (pyrosis, disphagia) and endoscopic features (length). HER2 status was studied by immunohistochemistry and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue. The end-points were the occurrence of progression and the time-to-progression (TTP) from the initial histologic lesion to the worst pathological pattern. Median age at diagnosis was 63 years (range 37–84). BO median length was 4.5 cm. Progression occurred in 11 of 21 patients and median TTP was 24 months. HER2 was overexpressed/amplified in 8 of 21 (38%) patients. HER2 overexpression/ amplification and the presence of dysplasia were statistically associated with progression (P= 0.038). This study provides evidence for a possible role of HER2 in the transition from dysplasia to ADC of the oesophagus. This fact could help in identifying patients at high risk of malignant transformation.

HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction

“…Previous studies of RTK expression in Barrett’s esophagus have been limited to an assessment of HER2, which is overexpressed in a minority of cases [3–5]. HER2 overexpression in this study was present in 3.4% of biopsy specimens, lower than the rate of HER1 or HER3 overexpression.…”

Magnitude of Missed Esophageal Adenocarcinoma After Barrett’s Esophagus Diagnosis: A Systematic Review and Meta-analysis

“…Four studies were population-based (median follow-up, 5.0 years), 2,3,9,21 4 were multicenter studies (median follow-up, 4.7 years), 27,29,39,42 and the remaining were single-center studies (median follow-up, 4.8 years). 19,20,22–26,28,30–38,40,41 Most studies reported or permitted a missed vs incident cutoff of exactly 12 months to be applied, with the exception of 2 studies reporting cutoffs of 9 and 6 months, 32,39 and 1 study for which only a cutoff of 14 months could be applied. 24 In these 3 studies, EAC (and HGD-EAC) detected before and after their respective cutoffs were classified as missed and incident, respectively.…”

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

“…38 The prevalence of HER2 positive has been found to be 15e38% in Barrett's oesophagus by utilizing various methods including PCR, 39 FISH and IHC. 40 An Italian study suggested that the presence of HER2 amplification in dysplastic lesions was statistically related to progression (P value ¼ 0.038), 40 highlighting the likely role of HER2 in the evolution from dysplasia to adenocarcinoma of the oesophagus. Similarly, HER2 overexpression seems to predict poor survival in Barrett's oesophagus-associated adenocarcinoma (P value ¼ 0.03).…”