Morphological features and molecular markers in rectal cancer from 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 trial: prognostic value and effects of preoperative radio (chemo) therapy

Eur J Cancer. 2008 Apr;44(6):791-7. doi: 10.1016/j.ejca.2008.02.023. Epub 2008 Mar 18.


In this study, the prognostic and/or predictive value of different proteins (cyclo-oxygenase 2 (COX-2), Ki67 and cleaved cytokeratin (CK) 18) and fibro-inflammatory changes which might be of importance for the response to treatment were evaluated using tissue micro arrays. Samples were obtained from a subset of 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 clinical trial, which randomised patients with rectal cancer to one of four arms treated with preoperative radiotherapy with or without pre- and/or postoperative chemotherapy. From our results, we can conclude that the addition of preoperative chemotherapy to radiotherapy led to significantly less COX-2 upregulation, less proliferation and more inflammation, as was seen in the resection specimen as well as less invasion and metastasis. For COX-2, Ki67 or cleaved CK18, no predictive or prognostic value could be identified. However, the fibro-inflammatory reaction after preoperative radiochemotherapy correlated with T-downstaging and seems to be an important factor for response.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclooxygenase 2 / metabolism*
  • Disease-Free Survival
  • Fibrosis
  • Humans
  • Immunohistochemistry
  • Keratin-18 / metabolism*
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Preoperative Care
  • Proctitis / pathology
  • Prognosis
  • Protein Array Analysis
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy
  • Rectum / pathology*


  • Keratin-18
  • Ki-67 Antigen
  • Cyclooxygenase 2