title: Maspin is a marker for early recurrence in primary stage III and IV colorectal cancer.
abstract: BACKGROUND
  Little is known about the factors that drive metastasis formation in colorectal cancer (CRC). Here, we set out to identify genes and proteins in patients with colorectal liver metastases that correlate with early disease recurrence. Such factors may predict a propensity for metastasis in earlier stages of CRC.
  
  
  METHODS
  Gene expression profiling and proteomics were used to identify differentially expressed genes/proteins in resected liver metastases that recurred within 6 months following liver surgery vs those that did not recur for >24 months. Expression of the identified genes/proteins in stage II (n=243) and III (n=176) tumours was analysed by immunohistochemistry on tissue microarrays. Correlation of protein levels with stage-specific outcome was assessed by uni- and multivariable analyses.
  
  
  RESULTS
  Both gene expression profiling and proteomics identified Maspin to be differentially expressed in colorectal liver metastases with early (<6 months) and prolonged (>24 months) time to recurrence. Immunohistochemical analysis of Maspin expression on tumour sections revealed that it was an independent predictor of time to recurrence (log-rank P=0.004) and CRC-specific survival (P=0.000) in stage III CRC. High Maspin expression was also correlated with mucinous differentiation. In stage II CRC patients, high Maspin expression did not correlate with survival but was correlated with a right-sided tumour location.
  
  
  CONCLUSIONS
  High Maspin expression correlates with poor outcome in CRC after spread to the local lymph nodes. Therefore, Maspin may have a stage-specific function possibly related to tumour cell dissemination and/or metastatic outgrowth.
authors.affiliation: Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 GX Utrecht, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Snoeren
authors.forename: B L
authors.initials: BL
authors.lastname: Emmink
authors.forename: M J G
authors.initials: MJ
authors.lastname: Koerkamp
authors.forename: S R
authors.initials: SR
authors.lastname: van Hooff
authors.forename: J A C M
authors.initials: JA
authors.lastname: Goos
authors.forename: W J
authors.initials: WJ
authors.lastname: van Houdt
authors.forename: M
authors.initials: M
authors.lastname: de Wit
authors.forename: A M
authors.initials: AM
authors.lastname: Prins
authors.forename: S R
authors.initials: SR
authors.lastname: Piersma
authors.forename: T V
authors.initials: TV
authors.lastname: Pham
authors.forename: E J
authors.initials: EJ
authors.lastname: Belt
authors.forename: H
authors.initials: H
authors.lastname: Bril
authors.forename: H B
authors.initials: HB
authors.lastname: Stockmann
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
authors.forename: R
authors.initials: R
authors.lastname: van Hillegersberg
authors.forename: F C
authors.initials: FC
authors.lastname: Holstege
authors.forename: C R
authors.initials: CR
authors.lastname: Jimenez
authors.forename: R J A
authors.initials: RJ
authors.lastname: Fijneman
authors.forename: O W
authors.initials: OW
authors.lastname: Kranenburg
authors.forename: I H M Borel
authors.initials: IH
authors.lastname: Rinkes
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015843:Serpins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C085344:SERPIN-B5; D015843:Serpins