M A Gordon1, H M Gundacker2, J Benedetti2, J S Macdonald3, J C Baranda4, W J Levin5, C D Blanke6, W Elatre1, P Weng1, J Y Zhou1, H J Lenz7, M F Press8. 1. Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles. 2. SWOG Statistical Center, Seattle. 3. Aptium Oncology, Inc., Los Angeles. 4. University of Kansas Cancer Center, Westwood. 5. Pfizer, Inc., San Diego. 6. Department of Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland. 7. Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA. 8. Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles. Electronic address: press@usc.edu.
Abstract
BACKGROUND: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. PATIENTS AND METHODS: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. RESULTS: HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2-amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. CONCLUSION: Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. CLINICAL TRIAL: INT-0116/SWOG9008 phase III.
BACKGROUND:Trastuzumab has been approved for patients with humanepidermal growth factor receptor 2 (HER2)-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. PATIENTS AND METHODS: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. RESULTS:HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2-amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. CONCLUSION:Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. CLINICAL TRIAL: INT-0116/SWOG9008 phase III.
Authors: Pamela L Kunz; Amirkaveh Mojtahed; George A Fisher; James M Ford; Daniel T Chang; Raymond R Balise; Charles D Bangs; Athena M Cherry; Reetesh K Pai Journal: Appl Immunohistochem Mol Morphol Date: 2012-01
Authors: Andreas H Marx; Lars Tharun; Johanna Muth; Ana-Maria Dancau; Ronald Simon; Emre Yekebas; Jussuf T Kaifi; Martina Mirlacher; Tim H Brümmendorf; Carsten Bokemeyer; Jakob R Izbicki; Guido Sauter Journal: Hum Pathol Date: 2009-03-09 Impact factor: 3.466
Authors: Hiroaki Nitta; Beatrice Hauss-Wegrzyniak; Megan Lehrkamp; Adrian E Murillo; Fabien Gaire; Michael Farrell; Eric Walk; Frederique Penault-Llorca; Masafumi Kurosumi; Manfred Dietel; Lin Wang; Margaret Loftus; James Pettay; Raymond R Tubbs; Thomas M Grogan Journal: Diagn Pathol Date: 2008-10-22 Impact factor: 2.644
Authors: Angela N Bartley; Mary Kay Washington; Christina B Ventura; Nofisat Ismaila; Carol Colasacco; Al B Benson; Alfredo Carrato; Margaret L Gulley; Dhanpat Jain; Sanjay Kakar; Helen J Mackay; Catherine Streutker; Laura Tang; Megan Troxell; Jaffer A Ajani Journal: Am J Clin Pathol Date: 2016-11-14 Impact factor: 2.493