Significance of human epidermal growth factor receptor 2 expression in colorectal cancer

Abstract

The aim of the present study was to evaluate the protein expression level of human epidermal growth factor receptor 2 (HER-2) using immunohistochemistry (IHC), and assess the association with clinicopathological parameters and the prognosis of patients with colorectal cancer (CRC). In addition, the current study observed the consistency between the levels of HER-2 protein expression determined by IHC and HER-2 gene amplification determined by fluorescence in situ hybridization (FISH) in the CRC samples. Overexpression of HER-2 and gene amplification were examined with semiquantitative standardized IHC in 878 formalin-fixed paraffin-embedded CRC samples, while 102 of these cases were analyzed with FISH. A total of 102 cases (11.6%), out of the 878 cases, were determined by IHC to overexpress HER-2. Of these, 25 cases were strongly positive (IHC3+), while 77 cases revealed moderate staining (IHC2+). HER-2 overexpression was more frequent in early-stage cases compared with advanced-stage cases of CRC (P<0.001). However, there was no association observed between HER-2 overexpression and clinicopathological parameters. FISH analysis revealed that 64% (16/25) of the IHC3+ cases had HER-2 gene amplification. By contrast, only 6.5% (5/77) of the IHC2+ cases, and none of the 20 randomly selected IHC0 or 1+ cases, demonstrated HER-2 gene amplification. Furthermore, no associations were observed between HER-2 overexpression or gene amplification with the survival time. Thus, the present study observed that HER-2 overexpression does not correlate with other clinicopathological data or the survival rate, with the exception of clinical stages. However, IHC3+ and 2+ cases should be further analyzed by FISH to assess the status of the HER-2 gene in CRC. Patients with HER-2 gene amplification may constitute as potential candidates for targeted therapy with trastuzumab.

Assessment of a HER2 scoring system for colorectal cancer: results from a validation study

“…[6][7][8][9][12][13][14][15][16][17][18][19][20] The present study is unique because the only study with an equally large sample size, albeit without clinical validation, reported much lower rates of both ERBB2 expression (2.7%) and positive amplification (1.6%). 8 This difference very likely resides in the fact that while our findings have been obtained on a primarily metastatic population, Heppner et al 8 tested only primary tumors using a different staining antibody (SP3) and a different in situ hybridization method (CISH), and employed gastric cancer criteria to test and score the samples.…”

“…Recently, we and others have found that activation of ERBB2 signaling causes resistance to anti-EGFR therapy in a fraction of metastatic colorectal patients, wild type for RAS codons 12-13. [10][11][12] Of more relevance for the clinic, we have demonstrated that the combination of the anti-ERBB2 monoclonal antibody trastuzumab and the dual EGFR/HER2 small-molecule inhibitor lapatinib, but not either drug alone, is effective in inducing durable tumor shrinkage in ERBB2-amplified metastatic CRC patient-derived xenografts. 10 Reasoning that ERBB2 corsivo could also represent a valuable therapeutic target in KRAS wild-type metastatic colorectal cancer patients resistant to anti-EGFR treatment, we designed the HERACLES trial, a phase II trial testing the combination of trastuzumab and lapatinib in ERBB2-positive metastatic colorectal cancer patients refractory to standard treatment, including cetuximab or panitumumab.…”

“…These are routinely used to establish ERBB2 status in breast and gastric cancer but have not been customized for colorectal cancer for which the reported rate for ERBB2 positivity ranges enormously from o1% to 450%. [6][7][8][9][12][13][14][15][16][17][18][19][20] The aim of the present study was to develop a validated ERBB2 scoring system for colorectal cancer with the goal of identifying ERBB2-positive patients suitable for enrollment in the HERACLES trial.…”

lncRNA PDIA3P regulates cell proliferation and invasion in non‑small cell lung cancer

“…The expression of Ki-67 in nude mice injected with A549 cells was measured using immunohistochemistry. The immunohistochemistry assay was conducted according to previous report (18). The sections were treated with rabbit polyclonal anti-Ki-67 antibody (1:100; cat.…”

Knockdown of KLK11 inhibits cell proliferation and increases oxaliplatin sensitivity in human colorectal cancer

“…Survival rates have increased with the introduction of irinotecan and oxaliplatin chemotherapy, as well as the use of targeted therapies in the past decade (6–8). Combined perioperative chemotherapy and surgery is a major therapeutic treatment for patients with initially resectable liver metastases from CRC (9–11). However, the development of drug resistance in cancer cells raises a major challenge to chemotherapy and restricts the anticancer efficacy of chemotherapeutic drugs (12–14).…”