Iakovlev Vladimir V, Arneson Nona C R, Wong Vietty, Wang Chunjie, Leung Stephanie, Iakovleva Gaiane, Warren Keisha, Pintilie Melania, Done Susan J
Division of Applied Medical Oncology, Toronto, Ontario, Canada.
Clin Cancer Res. 2008 Jul 15;14(14):4446-54. doi: 10.1158/1078-0432.CCR-07-4960.
In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis.
Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes.
Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05).
Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.
在寻找新靶点的过程中，先前已对导管原位癌（DCIS）和浸润性导管癌（IDC）的基因组进行了比较；然而，与癌症进展相关的基因组改变难以识别。我们假设，通过比较具有更广泛行为范围的病变（从纯DCIS到伴有淋巴结转移的IDC），可以检测到重大事件。
通过自我杂交测试校准的阵列比较基因组杂交技术，用于研究6例纯DCIS和17例与IDC配对的DCIS病例，其中8例肿瘤已扩散至局部淋巴结。
纯DCIS的基因组复杂性略高于浸润性肿瘤的DCIS和IDC成分。后两者在肿瘤之间以及同一肿瘤的成分之间表现出相似性，与纯DCIS相比，有几个区域被优先检测到。伴有淋巴结转移的IDC作为一个组显示出基因组图谱的相似性。17q22 - 24.2区域的扩增与更高的组织学分级、较大的IDC大小、淋巴管/血管侵犯以及淋巴结转移相关（P < 0.05）。
我们的研究结果表明，DCIS和IDC与特定的基因组事件相关。与IDC相关的DCIS在基因组上与浸润成分相似，因此可能代表具有高侵袭潜能的克隆或通过导管扩散的浸润性癌。具体而言，17q22 - 24.2区域的扩增是一个候选区域，当在DCIS中检测到时，可作为侵袭的预测指标进一步测试；当在DCIS或IDC中检测到时，可作为淋巴结转移的预测指标。
