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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Translational Research and Biomarkers

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

Authors: Kathrin Mutze, Rupert Langer, MD, Karen Becker, MD, Katja Ott, MD, Alexander Novotny, MD, Birgit Luber, PhD, Alexander Hapfelmeier, Martin Göttlicher, MD, Heinz Höfler, MD, Gisela Keller, PhD

Published in: Annals of Surgical Oncology | Issue 12/2010

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Histone Deacetylase (HDAC) 1 and 2 Expression and Chemotherapy in Gastric Cancer
Authors
Kathrin Mutze
Rupert Langer, MD
Karen Becker, MD
Katja Ott, MD
Alexander Novotny, MD
Birgit Luber, PhD
Alexander Hapfelmeier
Martin Göttlicher, MD
Heinz Höfler, MD
Gisela Keller, PhD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1182-1

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