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Immunohistochemistry for Histone H3 Lysine 9 Methyltransferase and Demethylase Proteins in Human Melanomas

Miura, Shinpei MD*,†; Maesawa, Chihaya MD*; Shibazaki, Masahiko PhD*; Yasuhira, Shinji PhD*; Kasai, Syuya PhD*; Tsunoda, Kanako MD; Maeda, Fumihiko MD; Takahashi, Kazuhiro MD; Akasaka, Toshihide MD; Masuda, Tomoyuki MD

The American Journal of Dermatopathology: March 2014 - Volume 36 - Issue 3 - p 211–216
doi: 10.1097/DAD.0b013e3182964e02
Original Study

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.

*Department of Tumor Biology, Institute of Biomedical Science; and

Departments of Dermatology and

Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.

Reprints: Chihaya Maesawa, MD, Department of Tumor Biology, Institute of Biomedical Science, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Morioka 028-3694, Japan (e-mail:

Supported in part by Grants-in-Aid for Scientific Research (22390071), the MIAST project, and a Grant-in-Aid for Strategic Medical Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

The authors declare no conflicts of interest.

© 2014 by Lippincott Williams & Wilkins.