• Cancer
• Cell adhesion
• Colon
• Dysplasia
• Endoscopy
• Esophagus
• Gastrointestinal

Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.

• dysplasia
• gastric cancer
• human epidermal growth factor receptor 2 (HER2)
• immunohistochemistry
• liquid biopsy
• neoplastic heterogeneity

• Biopsy
• Esophageal cancer
• Gastric cancer
• Gastroesophageal cancer
• HER2
• Immunohistochemistry
• Resection

Overexpression of human epidermal growth factor receptor 2 protein (Her-2) in Barrett neoplasia is significant for targeted therapy with trastuzumab. Here, we studied the frequency of Her-2 overexpression in Barrett adenocarcinoma and precursor lesions. Retrospective formalin-fixed paraffin-embedded tissue samples of 25 normal (NM) esophageal mucosa, 50 Barrett esophagus (BE) without dysplasia, 49 BE with low-grade dysplasia (LGD), 50 BE with high-grade dysplasia (HGD), and 50 invasive adenocarcinoma (ICA) were used. A BE tissue microarray was built and analyzed by Her-2 immunohistochemistry (IHC) and Her-2 dual in situ hybridization (DISH). Her-2 IHC expression was negative in NM and low in 26% of BE (IHC score: 1+) and in 24.5% of LGD (IHC score: 1 to 2+). Her-2 overexpression was seen in 28% of HGD and in 24% of ICA (IHC score: 2 to 3+). Her-2 DISH was negative in NM and BE but positive in 6% of LGD, 20% of HGD, and 18% of ICA. Differences in Her-2 DISH positivity between NM and HGD or ICA were statistically significant (P = 0.02), but those between NM and LGD or HGD and ICA were not (P = 0.2). Although Her-2 overexpression results in ICA were similar to previous reports, the finding of 28% in HGD was unexpected and may have clinical implications. Positive Her-2 DISH in 6% of LGD is novel, suggesting a role of Her-2 during BE progression.

Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett’s esophagus.

• Barrett’s esophagus
• Esophageal adenocarcinoma
• Gastroesophageal reflux disease
• Dysplasia
• Biomarkers
• Endoscopic imaging