Prognostic impact of HER2, EGFR, and c-MET status on overall survival of advanced gastric cancer patients

Abstract

Background This study was conducted to investigate whether human epidermal growth factor receptor 2 (HER2) status, epidermal growth factor receptor (EGFR) status, and c-MET status are independent prognostic factors for advanced gastric cancer patients who received standard chemotherapy. Method Unresectable or recurrent gastric or gastroesophageal junction cancer patients with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. Formalin-fixed paraffin-embedded tumor samples were examined for HER2, EGFR, and c-MET status using immunohistochemistry (IHC). Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as an IHC score of 3? or an IHC score of 2?/ FISH positive for HER2, and an IHC score of 2? or 3? for both EGFR and c-MET. Results Of the 293 patients from nine institutions, 43 (15 %) were HER2 positive, 79 (27 %) were EGFR positive, and 120 (41 %) were c-MET positive. Ten patients (3 %) showed positive co-expression of HER2, EGFR, and c-MET. After a median follow-up time of 58.4 months with 280 deaths, there was no significant difference in overall survival (OS) in terms of HER2 and EGFR status. However, there was a significant difference in OS between c-MET-positive and c-MET-negative patients [median, 11.9 months vs 14.2 months; hazard ratio, 1.31 (95 % confidence interval, 1.03-1.67); log-rank P = 0.024]. 123Gastric Cancer (2016( ) 19:183-191 DOI 10.1007 Multivariate analysis also showed that c-MET positivity was still a prognostic factor for OS [hazard ratio, 1.30 (95 % confidence interval, 1.02-1.67); P = 0.037]. Conclusions The study suggested that c-MET-positive status had poor prognostic value. These data could be used as the basis for future clinical trials for targeting agents for advanced gastric cancer patients.

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts

“…Epidermal growth factor receptor (EGFR) overexpression was observed in 27%-44% of primary gastric tumors, and is reported to be an indicator of poor prognostic outcome and, hence, an important therapeutic target. 4 Cetuximab (CET; Erbitux ® , Merck, Darmstadt, Germany) is a chimeric IgG monoclonal antibody (MAb) approved by the US Food and Drug Administration for colorectal carcinoma and head and neck cancers that has also shown clinical benefit toward advanced/metastatic gastric adenocarcinoma in combination with other chemotherapeutic agents as a first-line treatment. [5][6][7] Researchers have been interested in exploring anticancer formulations in the form of nanomedicines, either as a combination of multiple drugs loaded into nanocarriers (combinatorial nanomedicines) or as drug-loaded nanocarriers that are actively targeted to specific overexpressed surface receptors such as EGFR (targeted nanomedicines) to improve the anticancer potential.…”

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

“…76,77 EGFR copy number gains associate with an increased risk of invasion and metastasis in solid tumors including GC, suggesting its potential significance as a prognostic marker. [78][79][80][81] As reported, there is a strong relationship between EGFR gene copy number, protein expression and chromosome 7 polisomy. 82 Oh et al 83 further observed that EGFR CNVs existed in a series of GC cases and discovered that it was associated with unfavorable prognosis.…”

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

“…EGFR signaling can involve a number of intracellular molecules such as extracellular signal-regulated kinase (ERK), cyclin D1 and β-catenin [51]. The presence of EGFR is detected in a wide range of cancer types (Table 3 [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77]). Normally, the EGFR gene is located on chromosome 7.…”