Clin Colorectal Cancer 2018 09 19;17(3):198-205. Epub 2018 May 19.
Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. Electronic address:
Purpose: To evaluate a prognostic and predictive value of HER2 amplification in patients with metastatic colorectal cancer (mCRC).
Patients And Methods: Patients with mCRC who underwent surgical resection of the primary tumor and who received best supportive care with or without palliative chemotherapy between 2005 and 2015 were included. HER2 immunohistochemistry was performed using formalin-fixed, paraffin-embedded primary tumor specimens. HER2 amplification was confirmed by fluorescence in-situ hybridization. The RAS and BRAF mutations were centrally assessed using a PCR-based method. Patients were divided into 4 subgroups: R (RAS mutant), B (BRAF mutant), H (wild-type RAS/BRAF with HER2 amplification), and W (wild-type RAS/BRAF without HER2 amplification). Overall survival (OS) and progression-free survival of anti-epidermal growth factor receptor (EGFR) therapy were assessed.
Results: Among 370 eligible patients, data of 359 were successfully analyzed. Fifteen tumors harbored HER2 amplifications, including 4 tumors with concomitant RAS mutation (group R). The number of patients in groups R, B, H, and W was 204, 13, 11, and 131, respectively. The median OS was 27.4 months, and the median follow-up time was 63.2 months. The median OS for groups R, B, H, and W was 24.0, 14.2, 19.9, and 39.1 months, respectively. The number of patients who received anti-EGFR therapy in groups R, B, H, and W was 17, 4, 5, and 49, respectively. Progression-free survival of anti-EGFR therapy was significantly shorter in groups R, B, and H than in group W.
Conclusion: HER2 amplification was predictive of anti-EGFR therapy response and appeared to be prognostic in mCRC patients.