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


CONCLUSIONS
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.
Villanacci
V
V
Department of Pathology, University of Brescia, Spedali Civili, Brescia, Italy. villanacci@spedalicivili.brescia.it
Rossi
E
E
Grisanti
S
S
Bassotti
G
G
Ferrari
V D
VD
Missale
G
G
Minelli
L
L
Cengia
P
P
Marini
G
G
Cestari
R
R
D000230:Adenocarcinoma / Q000737:chemistry / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000150:complications*; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab