Type IV collagen as a tumour marker for colorectal liver metastases

Eur J Surg Oncol. 2011 Jul;37(7):611-7. doi: 10.1016/j.ejso.2011.04.010. Epub 2011 May 28.


Background: About 50% of patients with primary colorectal cancer (CRC) will develop liver metastases (CLM). Currently, carcinoembryonic antigen (CEA) is the most common tumour marker for CRC and CLM. However, the sensitivity and specificity of this marker is not optimal, as almost 50% of patients have tumours that do not produce CEA. Therefore there is a need for better markers for CRC and CLM.

Methods: The circulating levels of type IV collagen were measured in patients with CLM, primary CRC and in healthy controls. The expression pattern of type IV collagen was studied by immunofluorescence in CLM and normal liver tissue. The metastatic volume of CLM in the liver was estimated from CT.

Results: In CLM tissue type IV collagen is highly expressed in the areas of desmoplasia. Patients with primary CRC (Dukes' A-C) did not show any increase in circulating type IV collagen compared to healthy controls. However, patients with CLM have significantly elevated levels of circulating type IV collagen when compared to patients with primary CRC and healthy controls. The levels of type IV collagen decreased during chemotherapy and increased at the time of disease progression. The circulating levels of type IV collagen seem to reflect the tumour burden in the liver.

Conclusions: Type IV collagen has the potential to be used as tumour associated biomarker for CLM. These results indicate the importance of interaction between cancer cells and the stroma in the tumour microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood*
  • Carcinoembryonic Antigen / blood
  • Collagen Type IV / blood*
  • Collagen Type IV / drug effects
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology*
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Liver / metabolism
  • Liver Neoplasms / blood*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Tumor Burden


  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Collagen Type IV
  • Leucovorin
  • Fluorouracil