Open AccessAberrant promoter CpG island hypermethylation of the adenomatosis polyposis coli gene can serve as a good prognostic factor by affecting lymph node metastasis in squamous cell carcinoma of the esophagus
Author(s) -
Kim Y. T.,
Park J.Y.,
Jeon Y. K.,
Park S. J.,
Song J. Y.,
Kang C. H.,
Sung S. W.,
Kim J. H.
Publication year - 2009
Publication title -
diseases of the esophagus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.115
H-Index - 63
eISSN - 1442-2050
pISSN - 1120-8694
DOI - 10.1111/j.1442-2050.2008.00862.x
Subject(s) - medicine , metastasis , esophagus , dna methylation , fhit , lymph node , lymph , cancer research , esophageal cancer , cancer , methylation , carcinoma , oncology , cpg site , pathology , carcinogenesis , gene , tumor suppressor gene , biology , gene expression , biochemistry
SUMMARY There has been no clear evidence demonstrating whether DNA hypermethylation can affect the prognosis of esophageal cancer. We collected tissue from 50 cases of squamous cell carcinoma of the esophagus and tested them for DNA hypermethylation using methylation‐specific polymerase chain reaction. CpG island hypermethylations were observed in 10% for p16, 34% for RARβP2, 46% for adenomatosis polyposis coli (APC), 14% for RASSF1A, 84% for FHIT, and 8% for hMLH1. APC promoter hypermethylation was frequently found in patients without lymph node metastasis compared with those with lymph node metastasis (62.5% : 30.8%, P = 0.025). The number of metastatic lymph nodes were lower in patients with APC promoter hypermethylation (0.87 ± 0.30 : 3.07 ± 0.72, P = 0.008). Excluding operative mortalities and incomplete resections, 42 patients were analyzed for long‐term outcome. During the mean follow‐up period of 35 months, 17 developed recurrence and 14 died of cancer. Ten patients died of other causes. In univariable analysis, unmethylation of APC ( P = 0.0015) and FHIT ( P = 0.0044), as well as presence of lymph node metastasis ( P = 0.0038), were risk factors for recurrence. In multivariable analysis, lymph nodes metastasis ( P = 0.050) and unmethylation of APC promoter ( P = 0.023) remained as significant risk factors. In conclusion, promoter hypermethylation of the APC gene is related to a lower number of metastatic lymph nodes and to superior prognosis in terms of recurrence, which suggests it might be involved in the process of lymph node metastasis in esophageal cancer.