Abstract
This study aimed at determining the incidence and clinical implications of HER2 status in primary colorectal cancer (CRC). HER2 status was investigated in two retrospective cohorts of 365 consecutive CRC patients (cohort 1) and 174 advanced CRC patients with synchronous or metachronous distant metastasis (cohort 2). HER2 status was determined by performing dual-color silver in-situ hybridization (SISH), mRNA in-situ hybridization (ISH), and immunohistochemistry (IHC). The incidence of HER2 protein overexpression (IHC 2+/3+) was approximately 6% (22 of 365 in cohort 1; 10 of 174 in cohort 2). HER2 gene amplification was observed in 5.8% of the patients from cohort 1 and 6.3% of the patients from cohort 2. HER2 gene amplification was more frequently observed in CRCs located in the rectum than in the right and left colon (P = 0.013 in cohort 1; P = 0.009 in cohort 2). HER2 status, determined by IHC, ISH, and dual-color SISH, was not significantly associated with aggressive CRC behaviour or patients' prognosis in both the cohorts. Of the combined cohort with a total of 539 cases, the concordance rate was 95.5% between dual-color SISH and IHC detection methods. On excluding equivocally immunostained cases (IHC 2+), the concordance rate was 97.7%. HER2 mRNA overtranscription, detected by ISH, significantly correlated with protein overexpression and gene amplification (P<0.001). HER2 gene amplification was identified in a minority of CRC patients with high concordance rates between dual-color SISH and IHC detection methods. Although HER2 status did not predict patients' prognosis, our findings may serve as a basis for future studies on patient selection for HER2 targeted therapy.
Highlights
Despite advances in surgical techniques and adjuvant chemotherapeutic regimens, colorectal cancer (CRC) remains one of the major leading causes of cancer-related deaths world over [1,2]
The purpose of this study was to identify the incidence of HER2positive status in two retrospective cohorts, including consecutive CRCs and advanced CRCs with distant metastasis, and to clarify their clinical significance
We observed that human epidermal growth factor receptor 2 (HER2) gene amplification and protein overexpression were found in about 6% of CRCs from both cohorts, CRCs with HER2 gene amplification were located more commonly in the rectum than in the right or left colon, HER2 status was not associated with aggressive clinicopathological features or worse prognosis, and the concordance rates between detection methods were very high
Summary
Despite advances in surgical techniques and adjuvant chemotherapeutic regimens, colorectal cancer (CRC) remains one of the major leading causes of cancer-related deaths world over [1,2]. Further improvements in understanding tumor biology and identifying oncogenic drivers have led to the development of new therapeutic targets [2,3]. Identification of biological markers for targeted therapy continues to be a high priority in human cancer treatment [4]. Anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment, including that with cetuximab and panitumumab, has been reported to improve progression-free survival in advanced CRC patients with wild-type KRAS [5,6,7]. Despite the undeniable therapeutic progress, a considerable proportion of cancer patients respond poorly to therapy, and therapeutic response cannot be exactly predicted. It is of great interest to identify molecular biomarkers for predicting outcome, therapeutic response, and potential therapeutic targets in CRC patients
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