Moguelet Philippe, Plassa Louis-François, Métayer Josette, Téniere Paul, Olschwang Sylviane, Frebourg Thierry, Legrand Martine, DE Thé Hugues, Janin Anne, Bertheau Philippe
Service de Pathologie et INSERM ERM 0220, 1 avenue Claude Vellefaux, 75010 Paris.
Service de Biochimie Hôpital Saint Louis AP-HP, 1 avenue Claude Vellefaux, 75010 Paris.
Cancer Genomics Proteomics. 2004 Jan-Feb;1(1):33-38. Epub 2004 Jan 1.
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract with an increased risk of malignancy. SMAD4 germline mutations account for about a third of JPS.
We describe, in the same family, the morphological and genetic aspects of two cases of JPS with colon cancer in one patient.
Both cases were characterised by diffuse colorectal and gastric involvement by typical juvenile polyps as well as "atypical" multilobulated and densely epithelial polyps with some dysplastic areas. A germline mutation of SMAD4 was demonstrated in both cases. SMAD4 protein and DNA analyses were performed on the colonic adenocarcinoma showing a lack of expression of SMAD4 protein and loss of heterozygosity at the SMAD4 locus.
These two exceptional familial cases underline the fact that the morphological features of JPS associated with SMAD4 mutations are different from those found in non SMAD4 mutated cases: polyps are more widespread in the upper GI tract with massive gastric polyposis and they have a dense epithelial component. This study also confirmed that SMAD4 genetic analysis is useful for the diagnosis of JPS and may be predictive of an increased risk of malignancy through inactivation of both alleles of SMAD4.
青少年息肉病综合征（JPS）是一种罕见的常染色体显性疾病，其特征是胃肠道出现多个错构瘤性息肉，且恶性肿瘤风险增加。SMAD4种系突变约占JPS的三分之一。
我们在同一家庭中描述了一名患有结肠癌的JPS患者的两例病例的形态学和遗传学特征。
两例病例的特征均为典型的青少年息肉弥漫性累及结肠和胃，以及具有一些发育异常区域的“非典型”多叶状和上皮密集型息肉。两例均证实存在SMAD4种系突变。对结肠腺癌进行了SMAD4蛋白和DNA分析，结果显示SMAD4蛋白表达缺失以及SMAD4基因座杂合性缺失。
这两例特殊的家族性病例强调了一个事实，即与SMAD4突变相关的JPS的形态学特征不同于非SMAD4突变病例：息肉在上消化道更广泛分布，伴有大量胃息肉，且具有密集的上皮成分。本研究还证实，SMAD4基因分析对JPS的诊断有用，并且可能通过SMAD4两个等位基因的失活预测恶性肿瘤风险增加。
