title: Frequency of HER-2 positivity in rectal cancer and prognosis.
abstract: In patients with advanced rectal cancer (cUICC II and III) multimodality therapy resulted in better long-term local tumor control. Ongoing clinical trials are focusing on therapy intensification to improve disease-free (DFS) and cancer-specific survival (CSS), the integration of biomarkers for prediction of individual recurrence risk, and the identification of new targets. In this context, we investigated HER-2, a member of the epidermal growth factor receptor family, whose expression pattern and role was unclear in rectal cancer. A total of 264 patients (192 male, 72 female; median age 64 y) received standardized multidisciplinary treatment according to protocols of phase II/III trials of the German Rectal Cancer Study Group. HER-2 status was determined in pretherapeutic biopsies and resection specimens using immunohistochemistry scoring and detection of silver in situ hybridization amplification. Tumors with an immunohistochemistry score of 3 or silver in situ hybridization ratios of ≥2.0 were classified HER-2 positive; these results were correlated with clinicopathologic parameters [eg, resection (R) status, nodal status ((y)pN)], DFS, and CSS. Positive HER-2 status was found in 12.4% of biopsies and in 26.7% of resected specimens. With a median follow-up of 46.5 months, patients with HER-2 positivity showed in trend a better DFS (P=0.1) and a benefit in CSS (P=0.03). The 5-year survival rate was 96.0% (HER-2 positive) versus 80.0% (HER-2 negative). In univariate and multivariate analyses, HER-2 was an independent predictor for CSS (0.02) along with the (y)pN status (P<0.00001) and R status (P=0.011). HER-2 amplification is detectable in a relevant proportion (26.7%) of rectal cancer patients. For the development of innovative new therapies, HER-2 may represent a promising target and should be further assessed within prospective clinical trials.
authors.affiliation: Department of General and Visceral Surgery, University Medical Center, Göttingen, Germany. lena.conradi@med.uni-goettingen.de
authors.forename: Lena-Christin
authors.initials: LC
authors.lastname: Conradi
authors.forename: Hanna
authors.initials: H
authors.lastname: Styczen
authors.forename: Thilo
authors.initials: T
authors.lastname: Sprenger
authors.forename: Hendrik A
authors.initials: HA
authors.lastname: Wolff
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.forename: Manuel
authors.initials: M
authors.lastname: Nietert
authors.forename: Kia
authors.initials: K
authors.lastname: Homayounfar
authors.forename: Jochen
authors.initials: J
authors.lastname: Gaedcke
authors.forename: Julia
authors.initials: J
authors.lastname: Kitz
authors.forename: Recca
authors.initials: R
authors.lastname: Talaulicar
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Michael
authors.initials: M
authors.lastname: Ghadimi
authors.forename: Peter
authors.initials: P
authors.lastname: Middel
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human