The relationship between the Glasgow Microenvironment Score and markers of epithelial-mesenchymal transition in TNM II-III colorectal cancer

Hum Pathol. 2022 Sep:127:1-11. doi: 10.1016/j.humpath.2022.05.012. Epub 2022 May 25.

Abstract

Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) markers in CRC have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumors resected between 2000 and 2007 from the Western Infirmary, Stobhill, and Gartnavel General Hospitals in Glasgow was used. Immunohistochemistry was performed for 5 markers of EMT: E-cadherin, β-catenin, Fascin, Snail, and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear β-catenin and membrane Zeb-1 were significant for worse cancer-specific survival (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.01-2.76, P < .05; HR 2.22, 95% CI 1.24-3.97, P < .01; and HR 2.00, 95% CI 1.07-3.77, P = .03, respectively). GMS 0 was associated with low membrane Fascin (P = .03), whereas membrane and cytoplasmic Fascin were observed to be highest in GMS 1, but lower in GMS 2. Nuclear β-catenin was lowest in GMS 0, but highest in GMS 2 (P = .03), in keeping with its role in facilitating EMT. Novel associations were demonstrated between GMS categories and markers of EMT, particularly β-catenin and Fascin, which require further investigation in independent cohorts.

Keywords: Colorectal cancer; Epithelial-Mmesenchymal transition (EMT); Survival; Tumor Microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor
  • Cadherins
  • Colorectal Neoplasms* / pathology
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Tumor Microenvironment
  • beta Catenin

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Cadherins
  • beta Catenin