title: Immunohistochemistry for histone h3 lysine 9 methyltransferase and demethylase proteins in human melanomas.
abstract: Methylation and demethylation of histone H3 lysine 9 (H3K9) play a role in the transcriptional regulation of several cancer-related genes and are closely associated with malignant tumor behavior. A novel study has recently demonstrated that SETDB1, a member of the H3K9 methyltransferases, accelerates tumor formation significantly in a zebrafish melanoma model. However, the expression of H3K9 methyltransferases including SETDB1 and demethylases has not been systematically examined in samples of human melanoma. Here, we used immunohistochemistry to examine the expression of the H3K9 methyltransferases, EHMT2 and SETDB1, and a H3K9 demethylase, LSD1, in 67 patients with melanoma. Overexpression of EHMT2, SETDB1, and LSD1 was observed in 14 (21%), 38 (57%), and 53 (79%) of the 67 patients, respectively. A significant relationship was observed between overexpression of EHMT2 or SETDB1 and aggressive tumor behavior such as lymph node metastasis and/or distant metastasis (P < 0.05), whereas no significant relationship was evident for LSD1 immunoreactivity. Univariate log-rank tests demonstrated that patients with melanoma overexpressing EHMT2 had a poorer outcome (P < 0.001), whereas overexpression of SETDB1 or LSD1 had no prognostic impact. These results suggest that overexpression of EHMT2 might be a prognostic marker in patients with melanoma.
authors.affiliation: *Department of Tumor Biology, Institute of Biomedical Science; and Departments of †Dermatology and ‡Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Miura
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibazaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuhira
authors.forename: Syuya
authors.initials: S
authors.lastname: Kasai
authors.forename: Kanako
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Maeda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Akasaka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006649:Histocompatibility Antigens / Q000096:biosynthesis*; D056466:Histone Demethylases / Q000096:biosynthesis*; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011496:Protein Methyltransferases / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006649:Histocompatibility Antigens; D056466:Histone Demethylases; C495195:KDM1A protein, human; D011496:Protein Methyltransferases; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human