Abstract
Although the positivity of human epidermal growth factor receptor 2 (HER2) is low in colorectal cancer (CRC), anti-HER2 is becoming a new target therapy in metastatic colorectal cancer (mCRC). However, assessment of the HER2 scoring system was still not established in CRC. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to the HER2 diagnostic criteria for gastroesophageal adenocarcinoma (GEA criteria) and the HERACLES diagnostic criteria (HERACLES criteria) in a large cohort of Chinese CRC patients. The HER2 positivity was 2.9% (43/1490) and 2.6% (39/1490) in CRCs based on the GEA criteria and the HERACLES criteria, and 3.7% (9/243) in mCRC according to both criteria. HER2 status was associated with primary tumor location (P = 0.037), regional lymph node metastasis (P = 0.035), and TNM stage (P = 0.022) in CRCs based on the HERACLES criteria. No such association was found based on the GEA criteria. Furthermore, HER2 positive only presented in patients with RAS gene wild type (P = 0.001). Significant difference was only observed between the HER2-positive and HER2-negative groups in terms of disease-free survival for stage II-III CRCs (P = 0.048) according to the HERACLES criteria, but not based on the GEA criteria. Our findings suggest that the frequency of HER2 overexpression or amplification was low in Chinese CRC patients, and provide a rationale for further evaluation of HER2 in CRC based on the HERACLES criteria and the HER2 diagnostic criteria for gastroesophageal adenocarcinoma.
Highlights
Colorectal cancer (CRC) is the third most common malignant neoplasm and the second leading cause of cancer-related deaths worldwide [1]
No significant difference was observed between the human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative groups in terms of progression-free survival (PFS) in metastatic colorectal cancer (mCRC) (P = 0.919) (Fig. 2c). In this large Chinese cohort study, we evaluated HER2 status in CRC based on two different criteria and found that HER2 positivity in colorectal adenocarcinoma was quite low in Chinese population, with a rate of 2.9% according to the HER2 diagnostic criteria for gastroesophageal adenocarcinoma, and a rate of 2.6% according to the HERACLES criteria
HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; FISH, fluorescent in situ hybridization status was associated with clinical variables and disease-free survival (DFS) in patients with stage II-III CRC according to the HERACLES criteria, yet, the results were not found according to the HER2 diagnostic criteria for gastroesophageal adenocarcinoma
Summary
Colorectal cancer (CRC) is the third most common malignant neoplasm and the second leading cause of cancer-related deaths worldwide [1]. It is estimated that 370,000 newly diagnosed cases of CRC and 180,000 deaths from CRC occurred in China in 2014 [2]. 20% of the patients with newly diagnosed CRC already have distant metastases at the time of diagnosis and for those without metastasis [3], they can be treated with curative approaches but still retain a high risk of recurrence (up to 50%) [4]. As such, advanced stage diseases and recurrences after curative treatment are a significant cause of death. Cetuximab and panitumumab, which are directed against the epidermal growth factor receptor (EGFR), are the most common monoclonal antibody used in metastatic colorectal cancer (mCRC) to prolong survival [4, 5].
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