Shin Sandra J, Simpson Peter T, Da Silva Leonard, Jayanthan Janani, Reid Lynne, Lakhani Sunil R, Rosen Paul Peter
Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA.
Am J Surg Pathol. 2009 Apr;33(4):496-504. doi: 10.1097/PAS.0b013e31818af361.
Microglandular adenosis (MGA) is an uncommon, benign breast lesion that is characterized by a proliferation of small uniform, round glands lined by a single layer of epithelial cells around open lumina with haphazard infiltrative growth in fibrous and fatty breast tissue. Although MGA usually has an indolent course, there is morphologic evidence that MGA can be a precursor for the development of intraductal and invasive ductal carcinoma. To investigate the possibility of such a transition, we studied 17 cases of MGA or atypical MGA some of which had given rise to carcinoma in situ (CIS) and/or invasive ductal carcinoma using the reticulin stain, immunohistochemistry (S-100, p63, Ki-67, and p53), and a molecular approach involving microdissection and high-resolution comparative genomic hybridization and MYC chromogenic in situ hybridization. MGA and carcinomas arising from MGA were typically negative for p63 and positive for S-100 and Ki-67 and occasionally positive for p53. High-resolution comparative genomic hybridization identified recurrent gains and losses in MGA (2q+, 5q-, 8q+, and 14q-) and atypical MGA (1q+, 5q-, 8q+, 14q-, and 15q-). Some examples of MGA and carcinomas arising from MGA harbored few gross chromosomal abnormalities whereas others had considerable genetic instability with widespread aberrations affecting numerous chromosomal arms. Such widespread genetic changes, together with recurrent loss of 5q and gain of 8q were reminiscent of those reported specifically for basal-like, estrogen receptor-negative, and BRCA1-associated breast tumors. Concordant genetic alterations were identified between MGA, atypical MGA, and higher risk lesions (CIS and invasive ductal carcinoma) and in some cases there was an accumulation of genetic alterations as cases "progressed" from MGA to atypical MGA, CIS, and invasive ductal carcinoma. The molecular data suggests that MGA, atypical MGA, and carcinoma arising in MGA in a single case were clonally related. This result implicates MGA as a nonobligate precursor for the development of intraductal and invasive ductal carcinoma.
微腺性腺病（MGA）是一种罕见的良性乳腺病变，其特征是在乳腺纤维和脂肪组织中，由单层上皮细胞围绕开放管腔排列的小而均匀的圆形腺体呈增生状态，并呈杂乱的浸润性生长。尽管MGA通常病程进展缓慢，但有形态学证据表明MGA可能是导管内癌和浸润性导管癌发生的前驱病变。为了研究这种转变的可能性，我们使用网状纤维染色、免疫组织化学（S-100、p63、Ki-67和p53）以及一种涉及显微切割、高分辨率比较基因组杂交和MYC显色原位杂交的分子方法，对17例MGA或非典型MGA病例进行了研究，其中一些病例已发展为原位癌（CIS）和/或浸润性导管癌。MGA及由MGA发展而来的癌通常p63呈阴性，S-100和Ki-67呈阳性，p53偶尔呈阳性。高分辨率比较基因组杂交确定了MGA（2q +、5q -、8q +和14q -）和非典型MGA（1q +、5q -、8q +、14q -和15q -）中反复出现的染色体增减。一些MGA及由MGA发展而来的癌的例子几乎没有明显的染色体异常，而其他例子则具有相当大的遗传不稳定性，广泛的畸变影响了许多染色体臂。这种广泛的基因变化，以及5q的反复缺失和8q的增加，让人联想到专门报道的基底样、雌激素受体阴性和BRCA1相关乳腺肿瘤的情况。在MGA、非典型MGA和高风险病变（CIS和浸润性导管癌）之间发现了一致的基因改变，在某些情况下，随着病例从MGA发展为非典型MGA、CIS和浸润性导管癌，基因改变会累积。分子数据表明，单个病例中的MGA、非典型MGA以及由MGA发展而来的癌在克隆上是相关的。这一结果表明MGA是导管内癌和浸润性导管癌发生的非必需前驱病变。
