Frequent PIK3CA activating mutations in nipple adenomas
Frequent PIK3CA activating mutations in nipple adenomas
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DOI：
10.1111/his.13043
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发表时间：
2017-01-01
期刊：
影响因子：
6.4
通讯作者：
Sheen, Yi-Shuan
中科院分区：
文献类型：
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作者：
Liau, Jau-Yu;Lee, Yi-Hsuan;Sheen, Yi-Shuan
目的：乳头腺瘤（NA）是一种罕见的发生在乳头的良性上皮肿瘤。组织学上，它表现出可变的，往往混合腺病样和常见的导管增生样生长模式。在形态学上，它类似于发生在乳腺实质中的其他良性增生性乳腺病变，这些病变已被证明在超过50%的病例中含有PIK 3CA、AKT 1或较不常见的RAS中的激活突变。方法：采用桑格测序法对24例NAs进行PIK 3CA、AKT 1、RAS和BRAF基因突变检测，并与组织学特征进行相关性分析。我们的研究结果表明，激活PIK 3CA突变被确定在15个NA中的8个（53%）具有主要的腺样模式，9个NA中的4个（44%）具有主要的常见导管增生样模式。一个具有PIK 3CA H1047 R突变的肿瘤也具有KRAS Q61 H突变。两个具有腺病样模式的肿瘤具有BRAF V600 E突变。总的来说，我们的系列中有一半（12/24，50%）的NAs有PIK 3CA突变，58%（14/24）有PIK 3CA，RAS或BRAF突变。结论：我们的数据表明，类似于其他良性增生性病变发生在乳腺实质中，激活PIK 3CA突变是非常常见的NAs，KRAS突变可能与PIK 3CA突变同时发生。此外，由于BRAF突变在以前的研究中尚未在良性增殖性病变中被鉴定，BRAF突变的NA似乎具有不同的发病机制。
Aims: Nipple adenoma (NA) is a rare benign epithelial tumour occurring in the nipple. Histologically, it exhibits variable and often mixed adenosislike and usual ductal hyperplasia-like growth patterns. Morphologically, it is similar to other benign proliferative breast lesions occurring in the breast parenchyma, which have been shown to harbour activating mutations in PIK3CA, AKT1 or, less frequently, in RAS in more than 50% of cases. In this study, we aimed to analyse the mutation status of PIK3CA, AKT1, RAS and BRAF in NAs and correlated the mutation status with the histological features.Methods and results: Mutation analysis of PIK3CA, AKT1, RAS and BRAF was performed in 24 NAs by Sanger sequencing. Our results showed that activating PIK3CA mutations were identified in eight of the 15 NAs (53%) with a predominantly adenosis-like pattern and four of the nine NAs (44%) with a predominantly usual ductal hyperplasia-like pattern. One tumour with a PIK3CA H1047R mutation also had a KRAS Q61H mutation. Two tumours with an adenosis- like pattern had BRAF V600E mutations. Overall, half of the NAs (12 of 24, 50%) in our series had PIK3CA mutations and 58% (14 of 24) had PIK3CA, RAS or BRAF mutations.Conclusions: Our data indicate that, similar to other benign proliferative lesions occurring in the breast parenchyma, activating PIK3CA mutations are very common in NAs, and KRAS mutation may occur concurrently with PIK3CA mutation. In addition, as BRAF mutation has not been identified in benign proliferative lesions in previous studies, BRAF-mutated NAs appear to have distinct pathogenesis.