Open Access

Association of histone deacetylase expression with histology and prognosis of ovarian cancer

  • Authors:
    • Mitsutake Yano
    • Masanori Yasuda
    • Mika Sakaki
    • Koji Nagata
    • Takashi Fujino
    • Eiichi Arai
    • Takahiro Hasebe
    • Masaki Miyazawa
    • Mariko Miyazawa
    • Naoki Ogane
    • Kosei Hasegawa
    • Hisashi Narahara
  • View Affiliations

  • Published online on: January 4, 2018     https://doi.org/10.3892/ol.2018.7726
  • Pages: 3524-3531
  • Copyright: © Yano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Histone deacetylase (HDAC) inhibitor is known to have a cytotoxic effect on ovarian cancer cell lines. The present study analyzed the association between immunohistochemical HDAC expression and clinicopathological findings, in particular, the association with histological type and effect of chemotherapy. The histology of the 201 ovarian cancers addressed was as follows: Serous carcinoma (SEC), 100 cases; clear cell carcinoma (CCC), 56 cases; endometrioid carcinoma (EMC), 36 cases; and mucinous carcinoma (MUC), 9 cases. Immunohistochemical analyses of HDACs 1, 2, 3, 4, 5, 6 and 7 expression levels were performed using tissue microarrays, composed of 201 primary tumors and 38 tumors following chemotherapy. Overexpression of HDAC1 was detected in the nucleus of all cases with MUC, followed by CCC (80%), SEC (73%), and EMC (53%). CCC specifically demonstrated HDAC7 expression in both the nucleus (27%) and the cytoplasm (54%), and HDAC6 expression in the nucleus (34%). The comparison between prior to and following chemotherapy revealed a nuclear expression increase in HDAC1 (76% vs. 92%; P=0.03) and HDAC7 (0.0 vs. 16%; P=0.01), and cytoplasmic expression increase in HDAC6 (40 vs. 74%; P=<0.01) and HDAC7 (16 vs. 66%; P=<0.01). HDAC1 nuclear expression adversely affected overall survival in SEC (P=0.02) and EMC (P=0.03), and HDAC7 cytoplasmic expression in CCC was associated with a poor prognosis (P=0.06). In multivariate analysis, HDAC6 nuclear expression was determined as a poor prognostic factor (hazard ratio=3.51; 95% confidence interval, 1.49 to 8.27, P=<0.01). In the subgroup analysis, HDAC6 nuclear expression was associated with a poor prognosis in CCC (P=0.07), International Federation of Obstetrics and Gynecology stage III/IV (P=0.07), and suboptimal surgery (P=<0.01). In conclusion, HDACs may be associated with the prognosis of ovarian cancers, depending on the histological subtypes, and upregulated following chemotherapy. HDAC1, 6 and 7 may therefor act as promising therapeutic targets in the future.
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March-2018
Volume 15 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yano M, Yasuda M, Sakaki M, Nagata K, Fujino T, Arai E, Hasebe T, Miyazawa M, Miyazawa M, Ogane N, Ogane N, et al: Association of histone deacetylase expression with histology and prognosis of ovarian cancer. Oncol Lett 15: 3524-3531, 2018
APA
Yano, M., Yasuda, M., Sakaki, M., Nagata, K., Fujino, T., Arai, E. ... Narahara, H. (2018). Association of histone deacetylase expression with histology and prognosis of ovarian cancer. Oncology Letters, 15, 3524-3531. https://doi.org/10.3892/ol.2018.7726
MLA
Yano, M., Yasuda, M., Sakaki, M., Nagata, K., Fujino, T., Arai, E., Hasebe, T., Miyazawa, M., Miyazawa, M., Ogane, N., Hasegawa, K., Narahara, H."Association of histone deacetylase expression with histology and prognosis of ovarian cancer". Oncology Letters 15.3 (2018): 3524-3531.
Chicago
Yano, M., Yasuda, M., Sakaki, M., Nagata, K., Fujino, T., Arai, E., Hasebe, T., Miyazawa, M., Miyazawa, M., Ogane, N., Hasegawa, K., Narahara, H."Association of histone deacetylase expression with histology and prognosis of ovarian cancer". Oncology Letters 15, no. 3 (2018): 3524-3531. https://doi.org/10.3892/ol.2018.7726