E-cadherin expression in patients with esophageal squamous cell carcinoma: promoter hypermethylation, Snail overexpression, and clinicopathologic implications.
Hypermethylation in the E-cadherin promoter region and expression of the transcription factor Snail were analyzed in 41 cases of esophageal squamous cell carcinoma (ESCC) and paired normal squamous epithelium by methylation-specific polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) to clarify the mechanism regulating E-cadherin deletion; 93 cases of ESCC were analyzed immunohistochemically to determine the clinicopathologic impact of E-cadherin deletion. Hypermethylation of the E-cadherin promoter and Snail overexpression were detected in 25 cases (61%) by methylation-specific PCR and 34 cases (83%) by RT-PCR, respectively. Reduced E-cadherin expression, observed immunohistochemically in 55 cases (59%), correlated with hypermethylation (P = .0011) but not Snail overexpression (P = .685). Hypermethylation and Snail overexpression correlated significantly with E-cadherin deletion (P = .0018). Snail overexpression was unrelated to clinicopathologic factors. Reduced E-cadherin expression correlated with tumor invasion (P = .019) and vascular invasion (P = .052) but not other factors. E-cadherin deletion had prognostic impact in univariate (P = .023) and multivariate (P = .034) analyses. E-cadherin deletion was regulated by hypermethylation and Snail expression. Examination of reduced E-cadherin expression is important for assessing biologic behavior, including clinical outcome, in patients with ESCC.
Takeno
Shinsuke
S
Department of Oncological Science (Surgery II), Faculty of Medicine, Oita University, Japan.
Noguchi
Tsuyoshi
T
Fumoto
Shoichi
S
Kimura
Yasuhiko
Y
Shibata
Tomotaka
T
Kawahara
Katsunobu
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D015820:Cadherins; D004268:DNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors