β-Catenin蛋白在散发性结直肠癌中的异常表达和基因突变

Aberrant expression and mutation of β-catenin in sporadic colorectal cancer

目的:观察β-Catenin蛋白在散发性结直肠癌(SCRC)中胞质胞核异常表达特征和基因突变发生率,并探讨其与临床病理的相关性.方法:用免疫组织化学EnVision二步法检测90例SCRC与22例散发性结直肠腺瘤标本的β-Catenin蛋白在胞质胞核中的异常表达.以PCR扩增和直接测序检测上述标本中β-Catenin基因突变.结果:正常结直肠黏膜中β-Catenin蛋白表达定位于细胞膜上,未见胞质胞核中的异常表达.SCRC中β-Catenin蛋白在胞质与胞核的异常表达率显著高于散发性腺瘤中的异常表达率(88.9%vs59.1%,41.1%vs18.2%,P<0.05).SCRC的β-Catenin异常胞质表达率与肿瘤生长方式,分化程度相关(P<0.05);胞核异常表达率在溃疡型生长高于在隆起型生长(50.0%vs26.5%,P<0.05).胞核异常表达往往出现在肿瘤的浸润前沿.90例SCRC中仅发现1例β-Catenin基因突变;22例散发性结直肠腺瘤中未检测出突变.结论:β-Catenin蛋白胞质胞核异常表达可能在SCRC的发生发展中起重要作用.在SCRC中β-Catenin基因突变可能不是β-Catenin蛋白异常表达的主要原因.

AIM：To observe the aberrant expression and mutation of β-catenin in sporadic colorectal cancer（SCRC）and explore their correlation with clinicopathological features. METHODS：Ninety SCRC samples and 22 sporadic colorectal adenoma samples were used in this study.The aberrant expression of β-catenin was detected by immunohistochemistry.PCR amplification and direct DNA sequencing were used to identify β-catenin gene mutations. RESULTS：In normal colorectal mucosa, β-catenin was distributed on the plasma membrane,without aberrant cytoplasmic and nuclear accumulation.The aberrant cytoplasmic and nuclear expression rates of β-catenin in SCRC were higher than those in sporadic colorectal adenomas（88.9%vs 59.1%and 41.1%vs 18.2%, respectively,P〈0.05）,respectively.The aberrant cytoplasmic expression of β-catenin was significantly correlated with tumor growth pattern and differentiation（P〈0.05）.The aberrant nuclear expression rate of β-catenin in ulcerative lesions was higher than that in protruding lesions（50.0% vs 26.5%,P〈0.05）.Aberrant nuclear expression of β-catenin was frequently observed in the invasive front of SCRC.β-catenin gene mutation was identified in one out of 90 SCRC samples, but was not identified in all sporadic colorectal adenoma samples. CONCLUSION：Aberrant cytoplasmic and nuclear expression of β-catenin may play an important role in the development and progression of SCRC.β-catenin mutation may not be the primary cause of aberrant β-catenin expression in SCRC.