Yoshida M, Sekine S, Ogawa R, Yoshida H, Maeshima A, Kanai Y, Kinoshita T, Ochiai A
Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.
1] Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan [2] Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Br J Cancer. 2015 May 12;112(10):1703-8. doi: 10.1038/bjc.2015.116. Epub 2015 Apr 2.
Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour.
Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing.
MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas.
MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background.
叶状肿瘤是一种罕见的乳腺纤维上皮性肿瘤，包括良性、交界性和恶性病变。尽管叶状肿瘤的分子基础在很大程度上仍不清楚，但最近一项外显子组研究发现，MED12突变是纤维腺瘤（一种与叶状肿瘤具有某些组织学特征的常见良性纤维上皮性肿瘤）中唯一反复出现的基因改变。
采用桑格测序法对46例乳腺叶状肿瘤和58例乳腺纤维腺瘤进行MED12突变分析。
46例叶状肿瘤中有37例（80%）检测到MED12突变。MED12突变在良性肿瘤（15/18，83%）、交界性肿瘤（12/15，80%）和恶性肿瘤（10/13，77%）中的发生率相似。58例纤维腺瘤中有36例（62%）也检测到MED12突变。这些突变在管内型（24/32，75%）和复杂型病变（4/6，67%）中较为常见，但在管周型病变中明显较少见（8/20，40%）。基于显微切割的分析表明，MED12突变在叶状肿瘤和纤维腺瘤的间质成分中均有出现。
无论肿瘤分级如何，MED12突变在乳腺叶状肿瘤中都很常见。叶状肿瘤和纤维腺瘤至少部分共享一个共同的遗传背景。
