Analysis of families with Lynch syndrome complicated by advanced serrated neoplasia: the importance of pathology review and pedigree analysis.
Analysis of families with Lynch syndrome complicated by advanced serrated neoplasia: the importance of pathology review and pedigree analysis.
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DOI：
10.1007/s10689-009-9238-8
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发表时间：
2009
期刊：
影响因子：
2.2
通讯作者：
Young, Joanne P.
中科院分区：
文献类型：
--
作者：
Walsh, Michael D.;Buchanan, Daniel D.;Walters, Rhiannon;Roberts, Aedan;Arnold, Sven;McKeone, Diane;Clendenning, Mark;Ruszkiewicz, Andrew R.;Jenkins, Mark A.;Hopper, John L.;Goldblatt, Jack;George, Jillian;Suthers, Graeme K.;Phillips, Kerry;Young, Graeme P.;Macrae, Finlay;Drini, Musa;Woods, Michael O.;Parry, Susan;Jass, Jeremy R.;Young, Joanne P.
Lynch综合征的鉴定得到了肿瘤免疫组化（IHC）错配修复（MMR）蛋白的出现以及对获得性体细胞BRAF突变在散发性MMR缺陷型结直肠癌（CRC）中作用的认识的极大帮助。然而，体细胞BRAF突变也可能存在于具有结肠直肠锯齿状息肉倾向的家族中的肿瘤中。在这些家族中受影响成员的亚组中，出现CRCs，其表现出MMR缺陷的明确证据，缺乏MLH1染色和高水平的微卫星不稳定性（MSI）。这可能导致这些家族被错误地归类为林奇综合征，或者相反，由于肿瘤中存在体细胞BRAF突变，个体被认为是“散发性”的。在这份报告中，我们描述了两个林奇综合征的家庭谁表现出几个这样的不一致。在一个家庭中，在来自不同受影响家庭成员的肿瘤中证明了MSH2和MLH1的IHC缺陷，这提供了令人困惑的诊断图片。在第二个家庭中，MLH1丢失被观察到在病变的MLH1突变携带者和那些谁显示正常MLH1种系序列。这两个家庭林奇综合征复杂的独立分离锯齿状瘤表型，这表明，在家庭，如这些，肿瘤和生殖系研究的几个关键成员，而不是一个单一的先证者，以澄清的风险谱。
The identification of Lynch syndrome has been greatly assisted by the advent of tumour immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and by the recognition of the role of acquired somatic BRAF mutation in sporadic MMR-deficient colorectal cancer (CRC). However, somatic BRAF mutation may also be present in the tumours in families with a predisposition to develop serrated polyps in the colorectum. In a subgroup of affected members in these families, CRCs emerge which demonstrate clear evidence of MMR deficiency with absent MLH1 staining and high-level microsatellite instability (MSI). This may result in these families being erroneously classified as Lynch syndrome or, conversely, an individual is considered “sporadic” due to the presence of a somatic BRAF mutation in a tumour. In this report, we describe two Lynch syndrome families who demonstrated several such inconsistencies. In one family, IHC deficiency of both MSH2 and MLH1 was demonstrated in tumours from different affected family members, presenting a confusing diagnostic picture. In the second family, MLH1 loss was observed in the lesions of both MLH1 mutation carriers and those who showed normal MLH1 germline sequence. Both families had Lynch syndrome complicated by an independently segregating serrated neoplasia phenotype, suggesting that in families such as these, tumour and germline studies of several key members, rather than of a single proband, are indicated to clarify the spectrum of risk.
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