Annals of Surgical Oncology

, Volume 17, Issue 12, pp 3336–3343 | Cite as

Histone Deacetylase (HDAC) 1 and 2 Expression and Chemotherapy in Gastric Cancer

  • Kathrin Mutze
  • Rupert Langer
  • Karen Becker
  • Katja Ott
  • Alexander Novotny
  • Birgit Luber
  • Alexander Hapfelmeier
  • Martin Göttlicher
  • Heinz Höfler
  • Gisela Keller
Translational Research and Biomarkers



Histone deacetylases (HDACs) modulate chromatin and may influence the effect of DNA-damaging drugs. We investigated HDAC1 and -2 expression in gastric carcinomas (GCs) for an association of patient outcome with conventional neoadjuvant chemotherapy. In vitro, HDAC inhibitors were evaluated as alternative treatment options.


HDAC1/2 expression was analyzed immunohistochemically in 127 pretherapeutic biopsy samples of neoadjuvant (platinum/5-fluorouracil) chemotherapy-treated GC patients and correlated with response and overall survival (OS). Chemosensitivity of four GC cell lines to cisplatin and the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and valproic acid was determined by XTT assays. Efficiencies of combined drug schedules were analyzed.


High expression of HDAC1/2 was found in 69 (54%) of 127 and 108 (85%) of 127 carcinomas, respectively, and was not associated with response or OS. In patients whose disease responded to therapy, high HDAC1 expression was associated with worse OS (P = 0.005). In cell lines, sequential treatment with SAHA and cisplatin showed synergistic effects irrespective of the initial cisplatin sensitivity.


HDAC1 and -2 expression is not suitable to predict response or survival for neoadjuvant-treated GC patients, but HDAC1 expression may be used for risk stratification in patients whose disease responds to therapy. Sequential treatment with SAHA and cisplatin may represent an alternative treatment option for GC patients.


Gastric Cancer Overall Survival Gastric Cancer Patient HDAC Inhibitor Gastric Cancer Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Wilhelm-Sander-Stiftung (grant 2006.035-1 to G.K. and K.O.).

Supplementary material

10434_2010_1182_MOESM1_ESM.doc (28 kb)
Supplementary material 1 (DOC 28 kb)
10434_2010_1182_MOESM2_ESM.eps (7.4 mb)
Supplementary Fig. 1 (a) Expression of HDAC1 in cell pellets of MKN28, MKN45, AGS and KATOIII cells determined by immunohistochemistry is shown. Original magnification 1:400 (b) Western blot analysis of HDAC1 expression in cell lysates. β-actin expression served as loading control (c) Densitometric analysis of the HDAC1 expression normalised to β-actin expression levels Supplementary material 2 (EPS 7591 kb)


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Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Kathrin Mutze
    • 1
  • Rupert Langer
    • 1
  • Karen Becker
    • 1
  • Katja Ott
    • 2
  • Alexander Novotny
    • 3
  • Birgit Luber
    • 1
  • Alexander Hapfelmeier
    • 4
  • Martin Göttlicher
    • 5
  • Heinz Höfler
    • 1
    • 6
  • Gisela Keller
    • 1
  1. 1.Institute of PathologyTechnische Universität MünchenMunichGermany
  2. 2.Department of SurgeryUniversity HeidelbergHeidelbergGermany
  3. 3.Department of SurgeryTechnische Universität MünchenMunichGermany
  4. 4.Medical Statistics and EpidemiologyTechnische Universität MünchenMunichGermany
  5. 5.Institute of ToxicologyHelmholtz-Zentrum MünchenOberschleissheimGermany
  6. 6.Institute of PathologyHelmholtz-Zentrum MünchenOberschleissheimGermany

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