title: The histological growth pattern of colorectal cancer liver metastases has prognostic value.
abstract: Little is known about the biological characteristics that determine the prognosis of colorectal cancer (CRC) liver metastases. In previous work we reported three different histological patterns of the tumour-liver interface of CRC liver metastases, termed the pushing, replacement and desmoplastic growth pattern (GP). The purpose of this study was to confirm differences in angiogenic and hypoxic properties of CRC liver metastases with different GPs in a large data set and to study the value of the GP as a prognostic factor. In 205 patients undergoing a resection of CRC liver metastases, the GP of the metastasis was determined using haematoxylin-eosin and Gordon Sweet's silver staining. The tumour cell proliferation fraction (TCP%), endothelial cell proliferation fraction (ECP%) and carbonic anhydrase 9 (CA9) expression were determined using immunohistochemistry. Standard clinicopathological data and overall survival were recorded. 27.8, 15.6, 34.6 and 17.6 % of liver metastases had a replacement, pushing, desmoplastic and mixed GP, respectively. Analyses of TCP%, ECP% and CA9 expression demonstrated that CRC liver metastases with a replacement GP are non-angiogenic, while the ones with a pushing GP are the most angiogenic with angiogenesis being, at least partially, hypoxia-driven. GP (pushing or not) was the only independent predictor of survival at 2 years. CRC liver metastases grow according to different GP patterns with different angiogenic properties. At 2 years of follow-up a GP with a pushing component was an independent predictor of poor survival, suggesting that the pushing GP is characterized by a more aggressive tumour biology. Further elucidation of the mechanisms and biological pathways involved in and responsible for the differences in GP between CRC liver metastases in different patients might lead to therapeutic agents and strategies taking advantage of this 2 year 'window of opportunity'.
authors.affiliation: Translational Cancer Research Unit, Augustinus Hospital, Oosterveldlaan 24, 2610, Wilrijk, Antwerp, Belgium. Gert.vandeneynden@gza.be
authors.forename: Gert G
authors.initials: GG
authors.lastname: Van den Eynden
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Bird
authors.forename: Ali W
authors.initials: AW
authors.lastname: Majeed
authors.forename: Steven
authors.initials: S
authors.lastname: Van Laere
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: Peter B
authors.initials: PB
authors.lastname: Vermeulen
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000556:secondary*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016622:Silver Staining
chemical_list: D000951:Antigens, Neoplasm; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases