title: Effect of neoadjuvant chemotherapy on HER-2 expression in surgically treated gastric and oesophagogastric junction carcinoma: a multicentre Italian study.
abstract: Predictors of response to neoadjuvant chemotherapy are not available for gastric and oesophago-gastric junction carcinoma. HER-2 over-expression in breast cancer correlates with poor prognosis and high incidence of recurrence. First aim of this study was to evaluate if the HER-2 expression/amplification is predictive of response to neoadjuvant chemotherapy in terms of pathologic regression. Secondary aim was to evaluate if HER-2 expression varies after neoadjuvant treatment. Thirty-five patients with locally advanced gastric or oesophago-gastric junction carcinoma underwent preoperative chemotherapy and surgical resection at San Raffaele Scientific Institute and Spedali Civili of Brescia. HER-2 expression/amplification was evaluated on every biopsy at diagnosis time and on every surgical sample after neoadjuvant chemotherapy. Pathologic response to chemotherapy was evaluated according to TNM classification (ypT status and ypN status) and Mandard's tumour regression grade classification. In our series 10 patients (28.6%) showed a reduction in HER-2 overexpression and in 6 of them (17.1%) HER-2 expression completely disappeared. Only three of the six patients with HER-2 disappearance had a complete pathological response to neoadjuvant chemotherapy. There was a strong correlation between HER-2 negativity on biopsy and absence of lymph node metastasis in surgical samples after neoadjuvant chemotherapy, irrespective of nodal status before chemotherapy. A direct correlation between HER-2 reduction after neoadjuvant chemotherapy and pathologic regression (primary tumour and lymph nodes) in surgical samples was found. HER-2 negativity may represent a predictor of pathologic response to neoadjuvant chemotherapy for gastric and oesophago-gastric junction adenocarcinoma. Neoadjuvant treatment can reduce HER-2 overexpression.
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, Milan, Italy. chiari.damiano@hsr.it.
authors.forename: Damiano
authors.identifier: http://orcid.org/0000-0003-3623-686X
authors.initials: D
authors.lastname: Chiari
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Orsenigo
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guarneri
authors.affiliation: Surgical Clinic, Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Baiocchi
authors.affiliation: Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Mazza
authors.affiliation: Department of Pathology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Albarello
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bissolati
authors.affiliation: Surgical Clinic, Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Molfino
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Staudacher
mesh_terms: D000328:Adult; D000368:Aged; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010446:Peptide Fragments / Q000032:analysis*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery*
chemical_list: C445779:HER-2-derived peptide 884-899; D010446:Peptide Fragments
keywords: Gastric carcinoma; HER-2; Neoadjuvant chemotherapy; Oesophago-gastric junction