Laboratory of Genomics and Molecular Biology, International Center of Research and Teaching, A.C. Camargo Hospital, São Paulo, SP, Brazil.
Transl Oncol. 2012 Apr;5(2):113-23. doi: 10.1593/tlo.11280. Epub 2012 Apr 1.
Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.
在乳腺导管癌（DC）进展过程中，上皮细胞中的基因表达谱改变主要发生在纯导管原位癌（DCIS）到同时存在浸润性导管癌（DCIS-IDC）的原位成分之间，这意味着侵袭的分子程序已经在侵袭前病变中建立。为了评估触发肿瘤发生的上皮细胞中早期的分子改变，并将其作为乳腺导管癌进展的预后标志物进行测试，我们通过逆转录定量聚合酶链反应分析了八个先前在具有不同恶性潜能的侵袭前病变、纯 DCIS 和 DCIS-IDC 的原位成分中上皮肿瘤细胞群体之间差异表达的基因。APC13 和 CLTCL1 的下调被证明是 DC 进展的早期事件，预示着侵袭的表现。在侵袭出现后，ANAPC13 的进一步下调也发生了，并且在侵袭性肿瘤样本中存在该蛋白与乳腺癌患者的总生存率和无病生存率较高相关。此外，ANAPC13 水平低的肿瘤显示出更高的拷贝数改变，在 1q（1q23.1-1q32.1）、8q 和 17q（17q24.2）区域有显著增益，这些区域在乳腺癌中显示出常见的不平衡，提示 ANAPC13 的下调导致该疾病中的基因组不稳定性。
