Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma
Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma
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DOI：
10.1155/2000/930246
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发表时间：
2000-01-01
影响因子：
3.2
通讯作者：
Werner, M
中科院分区：
文献类型：
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作者：
Aubele, M;Cummings, M;Werner, M
有证据表明，乳腺癌是一种异质性疾病的表型以及分子生物学。到目前为止，在潜在的前体病变，如导管增生（DH）和导管原位癌（DCIS）的分子生物学水平上的异质性尚未进行研究。在这项研究中，我们应用比较基因组杂交（CGH）福尔马林固定，石蜡包埋的乳腺组织DH和DCIS，邻近浸润性导管癌（IDC），筛选这些潜在的前体病变的全基因组染色体不平衡。使用激光显微切割从切片中选择纯细胞群。通过简并寡核苷酸引物PCR（DOP-PCR）扩增分离的DNA，并进一步处理用于CGH分析。研究来自4名患者的多个样本（n=25），我们发现DH中已经存在平均5.6 +/- 0.9（平均值+/- SEM）染色体不平衡。在12个DCIS病变中，发现平均10.8（+/- 0.9）个畸变，4个相邻IDC病变中发现14.8（+/- 0.8）个畸变。与组织病理学序列平行的染色体变化数量的增加证实了这一假设，即癌可能是通过从正常上皮到增殖上皮的连续进展并最终发展成癌的。然而，在来自同一患者的每个实体的多个样本中鉴定出异质性结果，主要在DCIS样本中的染色体区域6p、9 p、11 q、16 p和17 q中，在DH样本中的3 p、16 p和17 q中。这种异质性结果在DH中最明显，在DCIS和IDC样本中较少。唯一的畸变始终发现在所有的样本-甚至在所有的DH样本-是扩增的20 q13 region.Our研究结果表明，激光显微切割，DOP-PCR和CGH的应用组合，可能有助于分析乳腺癌的发生途径，在合适的组织学材料。然而，到目前为止，还不清楚如何处理异质性结果，这使得识别相关变化更加困难。设置阈值并仅评估大多数样本中存在的染色体变化可能是一种可能性。然而，这涉及到不常见但可能重要的畸变可能被遗漏的风险。http://www.esacp.org/acp/2000/20-1/aubele.htm
There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin-fixed, paraffin-embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser-microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and further processed for CGH analysis.Investigating multiple samples (n=25) from four patients we found an average of 5.6 +/- 0.9 (mean +/- SEM) chromosomal imbalances already present in DH. In the twelve DCIS lesions an average of 10.8 (+/- 0.9) aberrations was identified with 14.8 (+/- 0.8) aberrations in the four adjacent IDC lesions. The increasing number of chromosomal changes in parallel with the histopathological sequence corroborate the hypothesis, that the carcinomas may have developed through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. However, heterogeneous results were identified in the multiple samples per entity from the same patient, demonstrated mainly in the DCIS samples in the chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and 17q. This heterogeneous findings were most pronounced within the DH and was less in the DCIS and IDC samples. The only aberration consistently found in all samples - even in all DH samples - was amplification of the 20q13 region.Our results demonstrate, that the applied combination of laser-microdissection, DOP-PCR and CGH, may serve to analyse breast carcinogenesis pathways in suitable histological material. However, so far, it is unclear how to handle heterogeneous results and these make identification of relevant changes more difficult. Setting a threshold and valuating only those chromosomal changes which are present in a majority of samples may be one possibility. This involves however, the risk that infrequent but possibly significant aberrations may be missed.Figures on http://www.esacp.org/acp/2000/20-1/aubele.htm.