Targeted therapy with trastuzumab in dysplasia and adenocarcinoma arising in Barrett's esophagus: a translational approach.

AIM: Human epidermal growth factor receptor (HER2) protooncogene, overexpressed/ amplified in preneoplastic lesions and in adenocarcinoma (ADC) of the esophagus, can be considered a target for treatment of esophageal dysplasia/ADC. The aim of this study was to evaluate the therapeutic role of the anti-HER2 monoclonal antibody, trastuzumab, in the management of ADC originating from HER2-positive Barrett's esophagus (BE). METHODS: Two patients with high-grade dysplasia and ADC of the esophagus after esophageal mucosectomy and no metastatic disease were studied. Patients were not eligible for radical surgery or chemo-radiotherapy because of age and comorbidities. HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. Additional immunohistochemical analyses were performed. The whole panel was analysed at baseline, after treatment and at follow-up. RESULTS: At baseline, the two patients showed HER-2 overexpression/amplification in all areas of dysplasia and ADC but not in BE. Six months after treatment no significant differences in terms of endoscopical and histological patterns of the disease were found. HER-2, EGFR, TOPOII-alpha and anti-ssDNA analysis demonstrated a down-regulation of these markers and increased apoptosis. CONCLUSION: This study demonstrates that this treatment is feasible. No clear evidence of dysplasia regression was observed. However, HER2 and TopoII-alpha downregulation and induction of apoptosis occurring 6 months after treatment encourages further investigation.

Immunological markers anti-saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: a helpful diagnostic tool.

AIM: Nowadays the diagnosis of inflammatory bowel disease (IBD) and the differentiation between Crohn disease (CD) and ulcerative colitis (UC) is still based on morphological changes identified at endoscopy, radiology, and histopathology. In 5-15% of cases this differentiation is not possible (diagnosed with indeterminate colitis). METHODS: We evaluated if recently developed commercial kits for the determination of anti-Saccharomyces Cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) are useful in differentiating cases of UC from CD diseases with a consequent reduced number of undefined colitis and improved clinical management. Sera from 56 consecutive patients with a clinical diagnoses of IBD were evaluated in a blinded fashion for the presence of ASCA IgA and IgG and ANCA IgG with 2 different diagnostic methods: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In our cases we observed good agreement between histopathological examination and laboratory results and the combined use of ASCA and ANCA yielded a correct diagnosis in 93% of patients with CD and in 97% of the UC patients. CONCLUSIONS: We confirm the value of the test for the diagnosis of CD and UC and the differentiation from other forms of colitis.