HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer
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Hanna Styczen1, Iris Nagelmeier2, Tim Beissbarth3, Manuel Nietert3, Kia Homayounfar1, Thilo Sprenger1, Ute Boczek1, Kathrin Stanek1, Julia Kitz4, Hendrik A. Wolff5, B. Michael Ghadimi1, Peter Middel2, Torsten Liersch1, Josef Rüschoff2, Lena-Christin Conradi1
1Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
2Targos Molecular Pathology, Pathology Nordhessen, Kassel, Germany
3Department of Medical Statistics, University Medical Center, Göttingen, Germany
4Department of Pathology, University Medical Center, Göttingen, Germany
5Department of Radiotherapy and Radiooncology, University Medical Center, Göttingen, Germany
Lena-Christin Conradi, e-mail: [email protected]
Keywords: colorectal cancer, HER-2, HER-3, targeted therapy, liver metastases
Received: January 25, 2015 Accepted: March 09, 2015 Published: April 13, 2015
Objective: In this study, we evaluate the frequency of HER-2 and HER-3 expression in liver metastases from patients with colorectal cancer (CRLM). We analyzed the potential of HER-2 and HER-3 as therapeutic targets and evaluated their prognostic value.
Patients and Methods: Overall 208 patients with CRLM were enrolled. HER-2 and HER-3 expression were determined in metastatic tissue of diagnostic punch biopsies (n = 29) or resection specimens (n = 179). The results of immunohistochemistry (IHC) scoring and In-situ-hybridization (ISH)-amplification were correlated with clinical parameters and for the 179 resected patients with cancer-specific (CSS) and overall survival (OS). The mean follow-up time was 56.7 months.
Results: Positivity of HER-2 status (IHC score 2+/ISH+ and IHC 3+) was found in 8.2% of CRLM. High expression of HER-3 (IHC score 2+ and IHC 3+) was detected in 75.0% of liver metastases. CSS after liver surgery was determined and was independent from the HER-2 status (p = 0.963); however HER-3 was prognostic with a favorable course for patients showing an overexpression of HER-3 (p = 0.037).
Conclusions: HER-2 overexpression occurs in only 8% of patients with CRLM but with 75% of cases HER-3 is frequently overexpressed in CRLM. Therefore, HER-2 and particularly HER-3 could serve as novel targets to be addressed within multimodal treatment approaches.
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