Molecular and clinico-pathological markers in rectal cancer: a tissue micro-array study

Int J Colorectal Dis. 2009 Feb;24(2):129-38. doi: 10.1007/s00384-008-0608-8. Epub 2008 Dec 3.

Abstract

Aims: The aims of the study were to study the effect of pre-operative treatment on the expression of tumour-related proteins and to correlate the expression of these proteins with response and survival of patients with advanced rectal cancer.

Materials and methods: Tissue micro-arrays from pre- and post-treatment biopsies of 99 patients with rectal cancer treated with pre-operative (chemo)radiotherapy were stained for epidermal growth factor receptor (EGFR), carbonic anhydrase IX, Ki67, vascular endothelial growth factor, cyclo-oxygenase 2 (COX-2) and cleaved cytokeratin 18 (c-CK18). Also, fibro-inflammatory alterations after treatment were evaluated.

Results: Pre-operative (chemo)radiotherapy caused fibro-inflammatory changes, a downregulation of proliferation (Ki67) and EGFR and an upregulation of apoptosis (cleaved CK18). Patients with a good regression during pre-operative treatment showed less proliferating and apoptotic cells in the resection specimen. Multivariate analysis showed that T downstaging, fibro-inflammatory changes in the resection specimen and COX-2 expression in the biopsy correlated with overall survival.

Conclusions: Pre-operative treatment has an effect on proliferation, apoptosis, inflammation and EGFR expression. The classical clinical parameters as well as fibro-inflammatory changes and COX-2 expression seem most valuable as predictors for survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Cluster Analysis
  • Cyclooxygenase 2 / metabolism
  • Disease-Free Survival
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Inflammation
  • Keratin-18 / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Preoperative Care
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Remission Induction
  • Tissue Array Analysis*

Substances

  • Biomarkers, Tumor
  • Keratin-18
  • Ki-67 Antigen
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • ErbB Receptors