Decreasing expression of glucose-regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma

Head Neck. 2016 Oct;38(10):1539-44. doi: 10.1002/hed.24471. Epub 2016 Jun 17.

Abstract

Background: The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various human cancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC.

Methods: A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki-67. Microvessel density was determined by immunohistochemical staining for CD34 and p53.

Results: Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression-free survival (PFS).

Conclusion: GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various human neoplasms. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1544, 2016.

Keywords: endoplasmic reticulum stress; glucose-regulated protein 78 (GRP78); immunoglobulin heavy chain binding protein (BiP); immunohistochemistry; laryngeal cancer; squamous cell carcinoma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Disease-Free Survival
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins