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Frequency of HER-2 Positivity in Rectal Cancer and Prognosis

Conradi, Lena-Christin MD*; Styczen, Hanna cand. med.*; Sprenger, Thilo MD*; Wolff, Hendrik A. MD; Rödel, Claus MD; Nietert, Manuel PhD§; Homayounfar, Kia MD*; Gaedcke, Jochen MD*; Kitz, Julia MD; Talaulicar, Recca*; Becker, Heinz MD*; Ghadimi, Michael MD*; Middel, Peter MD; Beissbarth, Tim PhD§; Rüschoff, Josef MD; Liersch, Torsten MD*

The American Journal of Surgical Pathology: April 2013 - Volume 37 - Issue 4 - p 522–531
doi: 10.1097/PAS.0b013e318272ff4d
Original Articles

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.

Departments of *General and Visceral Surgery


§Medical Statistics

Institute for Pathology, University Medical Center, Göttingen

Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany

L-C.C. and H.S. share first authorship.

Roche Diagnostics provided detection kits for the immunohistochemical staining.

Conflicts of Interest and Source of Funding: Supported by the Deutsche Forschungsgemeinschaft (KFO 179-2). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Lena-Christin Conradi, MD, Department of General and Visceral Surgery, University Medical Center, Robert-Koch-Str. 40, 37075 Göttingen, Germany (e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.