Cao Dengfeng, Polyak Kornelia, Halushka Marc K, Nassar Hind, Kouprina Nina, Iacobuzio-Donahue Christine, Wu Xinyan, Sukumar Saraswati, Hicks Jessica, De Marzo Angelo, Argani Pedram
Departments of Pathology and Immunology, Washington University, St Louis, MO, USA.
Breast Cancer Res. 2008;10(5):R91. doi: 10.1186/bcr2189. Epub 2008 Oct 27.
Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed.
We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR).
We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RT-PCR analysis of the index case.
We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS.
尽管传统上小叶原位癌（LCIS）被视为乳腺癌风险的标志物，但最近的临床、病理和基因分析支持了LCIS是浸润性小叶癌的低风险直接前体这一概念。尚未对LCIS进行全基因组表达谱分析。
我们使用基因表达序列分析（SAGE）对一例独特的形成肿块的LCIS病例的综合基因表达谱进行了分析。这个SAGE文库可在网上公开获取。通过将LCIS的基因表达谱与良性乳腺上皮和基质的基因表达谱进行比较，我们确定了在LCIS中上调和下调的几个基因。通过免疫组织化学在蛋白质水平以及通过定量逆转录聚合酶链反应（RT-PCR）在RNA水平对LCIS中先前未研究的选定基因的差异表达进行了验证。
相对于正常乳腺上皮和基质，我们发现LCIS中紧密连接蛋白4下调，基质金属蛋白酶9过表达。我们分别通过免疫组织化学在另外一系列11例和19例LCIS病例中验证了这些发现。通过对索引病例的定量RT-PCR分析进一步证实了基质金属蛋白酶9的过表达。
我们创建了首个LCIS的全基因组表达谱，并证明了细胞连接蛋白下调（预期结果）和基质金属蛋白酶9过表达（意外结果）。作为在线资源提供的这些数据的进一步分析应有助于对LCIS进行进一步的分子特征描述。
