Adduci Kelly M, Annis Caroline E, DeVries Sandy, Chew Karen L, Boutin Jennifer, Magrane Gregg, Ljung Britt-Marie, Waldman Frederic M, Esserman Laura J
Department of Surgery, University of California San Francisco, San Francisco, CA 94143-0808, USA.
Cancer. 2007 Jun 25;111(3):185-91. doi: 10.1002/cncr.22690.
Ductal lavage (DL) does not routinely identify cytologically malignant cells. For this study, the authors asked whether molecular analyses of DL specimens from women with cancer would identify abnormal cells, even if they appeared cytologically normal.
DL was performed and yielded fluid in 29 of 45 consenting women who were undergoing breast cancer surgery. Array comparative genomic hybridization (CGH) was performed on the corresponding tumor tissue from 14 women. There was no single, common alteration; thus, bacterial artificial chromosome-specific fluorescence in situ hybridization (FISH) probes were selected based on CGH alterations.
FISH copy number changes were detected in tumor sections in 9 women. In the corresponding 9 DL samples, 1 sample was clearly malignant on cytology, 1 showed marked atypia, 1 showed mild atypia, and the rest were benign. Five of the 9 DL samples had epithelial cells that showed genetic changes identical to those observed in the tumor by FISH. The remaining 4 of 9 DL samples that did not show molecular changes were probably (N = 1) or possibly (N = 3) from the same duct as the tumor.
Although only 11% of the DL samples were identified as malignant cytologically, 55% showed molecular changes that were identical to those observed in the tumor. FISH was more sensitive for finding tumor in DL specimens than cytology. However, the ductal system in which the tumor was located did not always yield fluid, limiting the sensitivity of DL. The results from this study showed that genetic changes can be detected in the absence of morphologic changes in cytologically benign cells, but the application will be limited without a better approach for acquiring cells and a common set of probes for detecting molecular abnormalities that are found in breast malignancies.
导管灌洗（DL）通常无法识别出细胞学上的恶性细胞。在本研究中，作者探讨了对癌症女性患者的DL标本进行分子分析是否能识别出异常细胞，即便这些细胞在细胞学上看似正常。
对45名同意参与研究且正在接受乳腺癌手术的女性进行DL操作，其中29名获得了灌洗液。对14名女性的相应肿瘤组织进行了阵列比较基因组杂交（CGH）。未发现单一的共同改变；因此，基于CGH改变选择了细菌人工染色体特异性荧光原位杂交（FISH）探针。
9名女性的肿瘤切片中检测到FISH拷贝数变化。在相应的9份DL样本中，1份在细胞学上明确为恶性，1份显示明显异型性，1份显示轻度异型性，其余为良性。9份DL样本中有5份的上皮细胞显示出与肿瘤中通过FISH观察到的相同的基因变化。9份未显示分子变化的DL样本中，其余4份可能（N = 1）或有可能（N = 3）与肿瘤来自同一导管。
尽管只有11%的DL样本在细胞学上被鉴定为恶性，但55%显示出与肿瘤中观察到的相同的分子变化。FISH在DL标本中发现肿瘤比细胞学更敏感。然而，肿瘤所在的导管系统并非总能获得液体，限制了DL的敏感性。本研究结果表明，在细胞学上良性的细胞中，即使没有形态学变化也能检测到基因变化，但如果没有更好的获取细胞的方法和一套用于检测乳腺恶性肿瘤中分子异常的通用探针，其应用将受到限制。
