Association between the overexpression of Her3 and clinical pathology and prognosis of colorectal cancer: A meta-analysis

Medicine (Baltimore). 2018 Sep;97(37):e12317. doi: 10.1097/MD.0000000000012317.

Abstract

Background: This study aimed to investigate the association between the overexpression of human epidermal growth factor receptor-3 (Her3) and the clinicopathological parameters and survival of patients with colorectal cancer (CRC).

Methods: Relevant studies on the overexpression of Her3 (measured by immunohistochemistry) and overall survival (OS) in patients with CRC were searched for in PubMed, EMBASE, and Cochrane Library. Published data were extracted and computed into odds ratios (ORs) for assessing the association of Her3 overexpression with tumor differentiation, tumor node metastasis (TNM) stage, position of colon cancer, sex, and age. Prognostic data were computed into hazard ratios (HRs) for OS.

Results: Eight studies including 1716 patients with CRC were included in this meta-analysis. The results revealed a significant association between Her3 overexpression and tumor differentiation [OR = 2.38; 95% confidence interval (95% CI): 1.76-3.22; P < .001], TNM tumor stage (OR = 0.71; 95% CI: 0.53-0.96; P = .03), and position of colon cancer (OR = 1.71; 95% CI: 1.28-2.27; P < .001). While patients with Her3 overexpression demonstrated a worse tumor response (OR = 0.31; 95% CI: 0.16-0.60; P < .001) and OS after treatment with cetuximab (HR = 1.86; 95% CI: 1.24-2.79; P = .003), they demonstrated better OS after symptomatic treatment (HR = 0.65; 95% CI: 0.50-0.85; P = .002). Her3 overexpression was not associated with sex (OR = 1.03; 95% CI: 0.83-1.28; P = .79), age (OR = 0.96; 95% CI: 0.75-1.24; P = .77), colon or rectum site (OR = 0.79; 95% CI: 0.44-1.43; P = .44), and total OS (HR = 1.09; 95% CI: 0.69-1.72; P = .72).

Conclusion: Her3 expression is associated with the clinical pathology and prognosis of CRC, which explains the nonefficacy of cetuximab treatment in patients with CRC.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Cetuximab / therapeutic use
  • Colon / pathology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Odds Ratio
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-3 / metabolism*
  • Rectum / pathology
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • ERBB3 protein, human
  • Receptor, ErbB-3
  • Cetuximab