Digital image analysis of breast epithelial cells collected by random periareolar fine-needle aspirates (RPFNA) from women at high risk for breast cancer taking hormone replacement and the aromatase inhibitor, letrozole, for six months
Digital image analysis of breast epithelial cells collected by random periareolar fine-needle aspirates (RPFNA) from women at high risk for breast cancer taking hormone replacement and the aromatase inhibitor, letrozole, for six months
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DOI：
10.1007/s10549-008-0274-0
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发表时间：
2009-06-01
影响因子：
3.8
通讯作者：
Bartels, Peter H.
中科院分区：
文献类型：
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作者：
Frank, Denise H.;Kimler, Bruce F.;Bartels, Peter H.
芳香化酶抑制剂目前正在评估作为预防剂在绝经后妇女的乳腺癌高风险。一项对42名接受激素替代疗法（HRT）的妇女进行的II期试验显示，Ki-67降低了66%，但细胞形态学或Masood评分没有变化。随后对样本子集进行的图像分析程序（核型分析）捕获了亚视觉信息，显示来曲唑治疗6个月后细胞异常减少。在本研究中，我们扩展了初步的核型分析研究，以确定核型分析测量的变化是否与II期试验中定量的风险生物标志物的变化相对应;其次，这些生物标志物是否可以一起用作个体病例中的反应标志物。使用了II期试验的巴氏染色切片。上皮细胞图像在CCD视频显微光度计上进行数字化，并使用半自动算法从该领域分割细胞核。分析的37例病例中有9例显示所有三种标志物的数值降低，尽管其中只有三种显示出足以被视为改善的实质性变化。然而，12例显示细胞学改善（Masood评分至少降低2分），另外13例显示Ki-67表达降低50%的中位基线值，另外5例显示核形态测定异常细胞减少至少10%。因此，37例病例中共有30例（81%）显示至少一种标志物改善。Ki-67%、核型异常和Masood评分变化之间无相关性，细胞学改善的标本也显示核形态异常的降低幅度更大。考虑到导致恶性肿瘤的机制的异质性，核染色质模式的定量分析可能是有价值的，作为一个全球性的，或整合，化学预防研究中的变化与其他标志物的生物标志物。需要与长期临床结果的相关性来验证信息生物标志物的有意义的组合。
Aromatase inhibitors are currently being evaluated as preventive agents in post-menopausal women at high risk for breast cancer. A phase II trial of 42 women on hormone replacement therapy (HRT) treated with letrozole for 6 months showed Ki-67 was reduced by 66% but showed no change in cytomorphology or Masood score. Subsequent image analytical procedures (karyometry) conducted on a subset of the samples captured subvisual information that showed reduced cellular abnormality after 6 months of letrozole. In the present study we expanded on the preliminary karyometry study to determine if the change in karyometric measurements corresponded to changes in risk biomarkers quantified in the Phase II trial; and secondly, whether these biomarkers might be used together to serve as markers of response in individual cases. Pap stained slides from the Phase II trial were used. Epithelial cell images were digitized on a CCD video-microphotometer and the nuclei were segmented from the field using a semiautomatic algorithm. Nine out of 37 cases analyzed showed a numerical decrease in all three markers, although only three of these exhibited changes substantial enough to be considered as an improvement. However, 12 cases showed improvement by cytology (a decrease in Masood score of at least 2), an additional 13 cases demonstrated a reduction in Ki-67 expression by 50% of the median baseline value, and an additional five cases exhibited a decrease of at least 10% in abnormal cells by nuclear morphometry. Thus, a total of 30 of 37 cases (81%) showed improvement in at least one marker. There was no correlation between changes in Ki-67%, karyometric abnormality, and Masood score change other than specimens that exhibited an improvement in cytology also displayed greater decreases in nuclear morphometry abnormalities. Given the heterogeneity of mechanisms leading to malignancy, the quantitative analysis of nuclear chromatin patterns may be valuable as a global, or integrating, biomarker of change in chemoprevention studies in conjunction with additional markers. Correlation with long term clinical outcome is needed to validate meaningful combinations of informative biomarkers.