Chaiyapan Walawee, Sangkhathat Surasak, Kanngurn Samornmas, Phukaoloun Monlika, Chiengkriwate Piyawan, Patrapinyokul Sakda
Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
Pediatr Surg Int. 2010 Feb;26(2):173-7. doi: 10.1007/s00383-009-2547-z. Epub 2009 Dec 18.
Molecular pathogenesis of gastrointestinal polyposis in Peutz-Jegher's syndrome (PJS) has been linked to the loss-of-function mutation of LKB1. Recent functional genetic studies have pointed out that LKB1 plays a physiological role in controlling the Wnt-signaling pathway and activation of the pathway as a consequence of LKB1 haploinsufficiency might be responsible for the development of harmatomatous polyps. This study aimed to look for immunohistochemical evidence of Wnt-signaling activation in PJS polyps.
Beta-catenin immunohistochemistry patterns were evaluated in gastrointestinal polyps from five cases of PJS. All patients were also evaluated for germline mutations of LKB1 and somatic mutations of beta-catenin in the polyps.
Four of the five cases had germline mutations of LKB1, including two novel mutations, a one-base insertion at codon 53 and a large deletion encompassing exon 3 (codon 136-155). PJS polyps from all patients showed generalized membrane and cytoplasmic localizations of beta-catenin along the mucosal endothelium. Polyps from two cases with LKB1 mutations revealed moderate-intensity nuclear staining in approximately 20 and 70% of the polyps.
The study offers additional evidence of Wnt-signaling activation in PJS polyp development at the tissue level, although the degree of up-regulation was not as high as has been found in Wnt-associated neoplasms.
黑斑息肉综合征（PJS）胃肠道息肉的分子发病机制与LKB1功能缺失突变有关。最近的功能遗传学研究指出，LKB1在控制Wnt信号通路中发挥生理作用，LKB1单倍体不足导致该通路激活可能是错构瘤性息肉发生的原因。本研究旨在寻找PJS息肉中Wnt信号激活的免疫组化证据。
对5例PJS患者的胃肠道息肉进行β-连环蛋白免疫组化分析。所有患者还进行了LKB1种系突变及息肉中β-连环蛋白体细胞突变的评估。
5例患者中有4例存在LKB1种系突变，包括2种新突变，一种是密码子53处的单碱基插入，另一种是包含外显子3（密码子136 - 155）的大片段缺失。所有患者的PJS息肉在黏膜内皮细胞上均显示β-连环蛋白的广泛膜性和胞质定位。2例LKB1突变患者的息肉中，分别约有20%和70%的息肉显示中等强度的核染色。
本研究为PJS息肉发生过程中Wnt信号激活提供了组织水平的额外证据，尽管上调程度不如在Wnt相关肿瘤中发现的高。
