title: The global histone modification pattern correlates with overall survival             in metachronous liver metastasis of colorectal cancer.
abstract: Post-translational histone modifications are known to be altered in cancer             tissues, and differences in the histone modification levels have recently been             used to predict the clinical outcome in patients with certain types of cancer.             In this study, we evaluated the immunohistochemical staining patterns of histone             H3 dimethylation and acetylation in metachronous liver metastasis of colorectal             carcinomas and examined its correlation with patient prognosis. Double 2 mm core             tissue microarrays were made from 54 paraffin-embedded samples of liver metastasis             from colorectal adenocarcinoma, and were examined by an immunohistochemical analysis             of histone H3 lysine 4 (H3K4) dimethylation, histone, H3 lysine 9 (H3K9) dimethylation             and histone H3 lysine 9 (H3K9) acetylation. Positive tumor cell staining for each             histone modification was used to classify patients into low- and high-staining             groups, which were then examined for correlations with the clinicopathological             parameters and clinical outcome. Dimethylation of H3K4 correlated with the tumor             histological type (P=0.043), and acetylation of H3K9 correlated with the tumor             histological type (P=0.016). In addition, lower levels of H3K4 dimethylation correlated             with a poor survival rate (P=0.035). The multivariate survival analysis showed             that the H3K4 dimethylation status is an independent prognostic factor for colorectal             cancer patients (P=0.011). We suggest that the pattern of histone modification             as detected by immunohistochemistry may be an independent prognostic factor for             metachronous liver metastasis of colorectal carcinomas.
authors.affiliation: Department of Gastro-intestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan. tamagawah@kcch.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamagawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshima
authors.forename: Manabu
authors.initials: M
authors.lastname: Shiozawa
authors.forename: Soichiro
authors.initials: S
authors.lastname: Morinaga
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Makoto
authors.initials: M
authors.lastname: Akaike
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Imada
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
mesh_terms: D000107:Acetylation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D006657:Histones; D008239:Lysine