Reduced acetylated histone H4 is associated with promoter methylation of the fragile histidine triad gene in resected esophageal squamous cell carcinoma.
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.
Tzao
Ching
C
Division of Thoracic Surgery, Cancer Epigenetics Laboratory, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, [corrected] tzao@yahoo.com
Sun
Guang-Huan
GH
Tung
Ho-Jui
HJ
Hsu
Han-Shui
HS
Hsu
Wen-Hu
WH
Wang
Yi-Ching
YC
Cheng
Yeung-Leung
YL
Lee
Shih-Chun
SC
D000107:Acetylation; D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D006657:Histones; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase