title: Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer.
abstract: We examined the potential of quantitative epidermal growth factor receptor (EGFR, synonym: c-erbB-1) and c-erbB-2 (synonym: HER2/neu) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy), followed by radical surgical resection, in patients with oesophageal cancer. Tissue samples were collected by endoscopic biopsy prior to treatment. RNA was isolated from biopsies and quantitative real-time reverse transcriptase-polymerase chain reaction assays were performed to determine c-erbB-1 and c-erbB-2 mRNA expression. Relative expression (tumour/paired normal tissue ratio standardised for beta-actin) was calculated for EGFR and c-erbB-2 mRNA. Expression levels were correlated with the objective histopathologic response in resected specimens. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumour cells, or in case a pathologically complete response was achieved. Expression of c-erbB-1 mRNA was not associated with the degree of histomorphological response. In contrast, the relative expression levels of c-erbB-2 mRNA >1 were not associated with major histopathologic responses (sensitivity 41.6%, specificity 100%), and 10 out of 36 (28%) patients could be unequivocally identified, whose tumours did not respond well to the delivered neoadjuvant radiochemotherapy (P<0.01). Quantitative expression levels of c-erbB-2, but not c-erbB-1 mRNA, in pretreatment biopsies appear to predict minor histopathologic response to our neoadjuvant radiochemotherapy protocol. This test could be used to prevent expensive, non effective and potentially harmful therapies in approximately one-fourth of our patients, and leads to a more individualised type of combined modality treatment.
authors.affiliation: Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Miyazono
authors.forename: R
authors.initials: R
authors.lastname: Metzger
authors.forename: U
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: S E
authors.initials: SE
authors.lastname: Baldus
authors.forename: J
authors.initials: J
authors.lastname: Brabender
authors.forename: E
authors.initials: E
authors.lastname: Bollschweiler
authors.forename: W
authors.initials: W
authors.lastname: Doerfler
authors.forename: R P
authors.initials: RP
authors.lastname: Mueller
authors.forename: H P
authors.initials: HP
authors.lastname: Dienes
authors.forename: T
authors.initials: T
authors.lastname: Aikou
authors.forename: A H
authors.initials: AH
authors.lastname: Hoelscher
authors.forename: P M
authors.initials: PM
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D066246:ErbB Receptors; D005472:Fluorouracil; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases