title: Global histone modification of H3K27 correlates with the outcomes in patients with metachronous liver metastasis of colorectal cancer.
abstract: BACKGROUND
  We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients.
  
  
  METHODS
  Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes.
  
  
  RESULTS
  The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047).
  
  
  CONCLUSIONS
  Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.
authors.affiliation: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi, Yokohama, Japan. rinta77-nosuke@amber.plala.or.jp
authors.forename: H
authors.initials: H
authors.lastname: Tamagawa
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.forename: M
authors.initials: M
authors.lastname: Numata
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Shiozawa
authors.forename: S
authors.initials: S
authors.lastname: Morinaga
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Y
authors.initials: Y
authors.lastname: Kameda
authors.forename: M
authors.initials: M
authors.lastname: Akaike
authors.forename: N
authors.initials: N
authors.lastname: Yukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Rino
authors.forename: M
authors.initials: M
authors.lastname: Masuda
authors.forename: Y
authors.initials: Y
authors.lastname: Miyagi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D008239:Lysine; D008297:Male; D008745:Methylation; D008875:Middle Aged; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D046888:Tissue Array Analysis
chemical_list: D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D008239:Lysine