Expression of beta-catenin and its mechanism of delocalization in intestinal-type early gastric cancer based on mucin expression.
The biological characteristics of intestinal-type early gastric cancers (ICs) differ based on mucin phenotypes. Beta-catenin delocalization is a predictive marker of aggressive biological behavior (submucosal invasion and lymph node metastasis) of ICs. The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes. Therefore, in the current study, the expression and mechanisms of delocalization of beta-catenin were elucidated on the basis of mucin phenotypes in 109 cases of ICs. There was increased cytoplasmic and nuclear beta-catenin expression (delocalization) in ICs with a predominant intestinal mucin phenotype (ICIP; 46.3% [25/54 cases]) compared to ICs with a predominant gastric mucin phenotype (ICGP; 20% [11/55 cases]). There were no beta-catenin or APC mutations in ICs. APC promoter hypermethylation was present in 49 of 105 (46.7%) cases of ICs. There was a significant relationship between APC promoter hypermethylation and beta-catenin delocalization in ICs, especially in ICIPs. There was no relationship between beta-catenin delocalization and APC gene loss of heterozygosity in ICs. In conclusion, we showed that beta-catenin delocalization was more evident in ICIPs, and APC promoter hypermethylation might play a role in delocalization of beta-catenin, especially in ICIPs.
Lee
Soo Han
SH
Department of Pathology, Pusan National University School of Medicine, Busan, Republic of Korea.
Kang
Hyun Jeong
HJ
Shin
Dong-Hun
DH
Cho
Duk-Yeon
DY
Song
Jin Mi
JM
Lee
Han Cheol
HC
Kim
Gwang Ha
GH
Song
Geun Am
GA
Sol
Mee Young
MY
Kim
Jee Yeon
JY
Choi
Kyung Un
KU
Lee
Chang Hun
CH
Huh
Gi Young
GY
Park
Do Youn
DY
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005743:Gastrectomy; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; D004273:DNA, Neoplasm; D009077:Mucins; D051176:beta Catenin