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Right arrow Esophagus - cancer

Ann Thorac Surg 2006;82:396-401
© 2006 The Society of Thoracic Surgeons

Original article: General thoracic

Reduced Acetylated Histone H4 is Associated With Promoter Methylation of the Fragile Histidine Triad Gene in Resected Esophageal Squamous Cell Carcinoma

Ching Tzao, MD, PhDa,*, Guang-Huan Sun, MD, PhDb, Ho-Jui Tung, PhDc, Han-Shui Hsu, MDd, Wen-Hu Hsu, MDd, Yi-Ching Wang, PhDe, Yeung-Leung Cheng, MD, PhDa, Shih-Chun Lee, MDa

a Division of Thoracic Surgery, Cancer Epigenetics Laboratory, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China
b Department of Surgery, Cancer Epigenetics Laboratory, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China
c Department of Humanity and Social Studies, National Defense Medical Center, Taipei, Taiwan, China
d Division of Thoracic Surgery, Veterans General Hospital, Taipei, Taiwan, China
e Department of Life Sciences, National Taiwan Normal University, Taipei, Taiwan, China

Accepted for publication March 20, 2006.

* Address correspondence to Dr Tzao, Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center 325, Section 2, Cheng Gong Rd, Nei Hu, Taipei, Taiwan 114 (Email: tzao{at}yahoo.com).

Presented at the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.

BACKGROUND: Promoter methylation inactivates expression of some important tumor suppressor genes and may be associated with histone modification. The fragile histidine triad (FHIT) gene is considered a tumor suppressor gene in different human epithelial cancers. We investigated whether FHIT methylation is associated with aberrant expression of Fhit protein and acetylated histone, and whether aberrant expression of Fhit protein and acetylated histone are related to prognosis after resection for esophageal squamous cell cancer.

METHODS: We analyzed FHIT methylation using methylation-specific polymerase chain reaction and Fhit protein and acetylated histone H4 using immunohistochemistry in 60 resected tumor specimens. Concordance analysis was performed between FHIT methylation and expression of Fhit as well as H4.

RESULTS: The FHIT methylation was observed in 33(55%) specimens, and the aberrant expression of Fhit and acetylated H4 was found in 42 (70%) and 40 (67%) specimens, respectively. Expression of aberrant Fhit correlated positively with tumor staging (p < 0.017) and nodal involvement (p = 0.004). Aberrant expression of acetylated H4 correlated positively with tumor staging (p < 0.001), nodal involvement (p < 0.001), and metastasis (p = 0.004). Concordance rates of 75% and 81.7% were present between promoter methylation of FHIT and expression of Fhit (p = 0.035) and acetylated H4 (p = 0.02).

CONCLUSIONS: Aberrant expression of Fhit and acetylated histone H4 are frequently associated with the presence of esophageal squamous cell carcinoma, and they are potential prognostic predictors for patients after resection of the tumor.






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