Hervieu V, Lepinasse F, Gouysse G, Guillaud O, Barel C, Chambonniere M-L, Bringuier P-P, Poncet G, Lombard-Bohas C, Partensky C, Chayvialle J-A, Scoazec J-Y
INSERM, Unité 45, IFR62, Faculté Laennec, Lyon, France.
J Clin Pathol. 2006 Dec;59(12):1300-4. doi: 10.1136/jcp.2005.035097. Epub 2006 May 26.
To clarify the role of beta-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of beta-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in beta-catenin expression.
229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of beta-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene.
The distribution of immunoreactive beta-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of beta-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months.
Immunohistochemically detectable nuclear accumulation of beta-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in beta-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.
为阐明β-连环蛋白在消化内分泌肿瘤发生中的作用，我们分析了一系列具有代表性的大量胃肠胰内分泌肿瘤，以确定β-连环蛋白变化的发生率和模式，并分析免疫组化检测到β-连环蛋白表达变化的肿瘤的临床和组织学特征。
采用免疫组化方法研究229例胃肠胰内分泌肿瘤（胃11例、十二指肠和壶腹29例、空肠和回肠51例、阑尾13例、结肠和直肠17例、胰腺108例），以评估β-连环蛋白的分布模式（膜性、胞质或核性）。分析DNA以检测CTNNB1基因第3外显子的突变。
免疫反应性β-连环蛋白蛋白的分布为膜性164例、胞质58例、核性7例。所有病例的CTNNB1基因第3外显子均未检测到突变。β-连环蛋白核内积聚的7例肿瘤均为大肿瘤（平均大小44（标准差（SD）18.5）mm）且伴有转移，其中5例有肝转移，Ki-67指数高（平均34%（SD 16.5%））且细胞周期蛋白D1过表达；6例检测到p53积聚。5例患者死于疾病；平均（SD）生存期为13.6（4.8）个月。
胃肠胰内分泌肿瘤中免疫组化可检测到的β-连环蛋白核内积聚并不常见，且通常与CNNTB1第3外显子突变无关。β-连环蛋白表达变化是消化内分泌肿瘤发生中的晚期事件，与肿瘤进展和扩散有关。
