MSH-6:: extending the reliability of immunohistochemistry as a screening tool in Muir-Torre syndrome
MSH-6:: extending the reliability of immunohistochemistry as a screening tool in Muir-Torre syndrome
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DOI：
10.1038/modpathol.3800997
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发表时间：
2008-02-01
期刊：
影响因子：
7.5
通讯作者：
Mahalingam, Meera
中科院分区：
文献类型：
--
作者：
Chhibber, Vishesh;Dresser, Karen;Mahalingam, Meera
Muir-Torre综合征的亚型，与遗传性非息肉病性结直肠癌等位，通常与错配修复蛋白MSH-2和/或MLH-1的种系突变相关。最近，在一个额外的错配修复蛋白MSH-6突变已被记录在Muir-Torre综合征患者。鉴于此，本研究的目的是确定皮脂腺肿瘤中相同的频率。总的来说，我们发现59%的皮脂腺肿瘤表现出至少一个错配修复蛋白基因的突变，这一患病率与以前其他人报道的相似。有趣的是，我们发现MSH-6是最常见的错配修复蛋白，丢失17/41（41%），其次是MSH-2 14/41（34%）和MLH-18/41（20%），并且每种的阳性预测值如下：MLH-1 88%，MSH-6 67%和MSH-2 55%。在我们的队列中，MSH-6生殖系突变的频率表明这并不是一个罕见的发现。17例有Muir-Torre综合征临床病史且仅MSH-6突变的患者中有3例显示微卫星稳定性的证据表明，生殖系MSH-6突变的表型不同于MLH-1和MSH-2突变的表型，进一步支持使用免疫组织化学作为Muir-Torre综合征患者的筛查工具，扩展组包括MSH-6。
The subtype of Muir-Torre syndrome, allelic to hereditary nonpolyposis colorectal cancer is typically associated with germline mutations in the mismatch repair proteins MSH-2 and/or MLH-1. More recently, mutation in an additional mismatch repair protein MSH-6 has been documented in a patient with Muir-Torre syndrome. Given this, the aim of the present study was to ascertain the frequency of the same in unselected sebaceous gland neoplasms. Overall, we found that 59% of sebaceous neoplasms exhibited a mutation in at least one mismatch repair protein gene-a prevalence rate similar to that reported previously by others. Of interest, we found MSH-6 to be the mismatch repair protein most commonly lost 17/41 (41%), followed by MSH-2 14/41 (34%) and MLH-18/41 (20%) and the positive predictive value of each were as follows: MLH-1 88%, MSH-6 67% and MSH-2 55%. The frequency of a MSH-6 germline mutation in our cohort indicates that it is not a rare finding. Evidence indicating microsatellite stability in three of 17 patients with a clinical history indicative of Muir-Torre syndrome and a mutation in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs from that of MLH-1 and MSH-2 mutations and further supports the use of immunohistochemistry as a screening tool in patients with Muir-Torre syndrome with an extended panel that includes MSH-6.