Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

Identification and characterisation of histological growth patterns of colorectal cancer liver metastases: (potential) role of  the  micro-environment (#45)

Gert G Van den Eynden 1 2 , Nigel Bird 1 3 , Martin Illemann 1 4 , Rikke L Eefsen 1 4 , Andrew Reynolds 1 5 , Pnina Brodt 1 6 , Ali W Majeed 1 3 , Gunilla Hoyer-Hansen 1 4 , Peter B Vermeulen 1 2
  1. on behalf of the Liver Metastasis Research Network, www.lmrn.org, International, collaborative research network
  2. Oncology Center - Augustinus Hospital, Wilrijk, Belgium
  3. Liver Research Group, University of Sheffield, Sheffield, UK
  4. Finsen Lab, Copenhagen, Denmark
  5. Tumour Biology Team, The Breakthrough Breast Cancer Research Center, London, UK
  6. Surgery, Oncology and Medicine, McGill University Health Center - Royal Victoria Hospital, Montreal, Canada

Worldwide, colorectal cancer (CRC) is the 4th and 3rd most common cancer in men and women, respectively. Of all patients, 25% present with liver metastases (LMs) and a further 25-50% will develop LMs during the 2 years following resection of the primary tumour. Remarkably little is known about the biological characteristics that determine the heterogeneity and prognosis of patients with LMs.

We have identified three different histological growth patterns (GPs) of LMs of solid tumours in general and of CRC in particular1 2 . In LMs with a desmoplastic GP the tumour is separated from the liver parenchyma by desmoplastic, inflammatory stroma. In the pushing type, the liver plates are compressed, running parallel to the tumour-liver interface without desmoplastic stroma and with only a mild inflammatory infiltrate. In the replacement GP tumour cells replace the hepatocytes without destruction of the liver architecture. There is no compression, no desmoplastic stroma or inflammatory infiltrate.

We have demonstrated significant biological differences associated with these GPs. Angiogenesis and hypoxia are significantly increased in pushing type LMs1 2 . The GP also differs according to the biological characteristics of the primary tumour, including the histological subtype and the differentiation grade2 . We also demonstrated different expression of the components of the plasminogen system in LMs with different GPs3 . Furthermore, we observed a remarkable tendency toward GP uniformity in multiple LMs arising in the same patient4 . Recently, we have demonstrated that the presence of a pushing component in the GP was an independent predictor for overall survival5 .

Collectively, these data  provide compelling evidence that the GPs in LMs of CRC are not a random phenomenon, but the apparent result of different tumour-micro-environment interactions. Current efforts focus on the molecular pathways underlying these GPs and the identification of GP-related biomarkers to guide the treatment of patients with CRC LMs.

  1. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. Vermeulen PB, Colpaert C, Salgado R, Royers R, Hellemans H, Van Den Heuvel E, Goovaerts G, Dirix LY, Van Marck E. J Pathol. 2001 Oct;195
  2. Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia. Stessels F, Van den Eynden G, Van der Auwera I, Salgado R, Van den Heuvel E, H
  3. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases. Illemann M, Bird N, Majeed A, Laerum OD, Lund LR, Danø K, Nielsen BS. Int J Cancer. 2009 Apr 15;124(8):1860-70.
  4. Histopathological growth pattern, proteolysis and angiogenesis in chemonaive patients resected for multiple colorectal liver metastases. Eefsen RL, Van den Eynden GG, Høyer-Hansen G, Brodt P, Laerum OD, Vermeulen PB, Christensen IJ, Wettergren A, Federsp
  5. The histological growth pattern of colorectal cancer liver metastases has prognostic value. Van den Eynden GG, Bird NC, Majeed AW, Van Laere S, Dirix LY, Vermeulen PB. Clin Exp Metastasis. 2012 Apr 3. Epub ahead of print