Chromatin phenotype karyometry can predict recurrence in papillary urothelial neoplasms of low malignant potential.
Chromatin phenotype karyometry can predict recurrence in papillary urothelial neoplasms of low malignant potential.
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DOI：
10.1155/2007/356464
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Bartels PH
中科院分区：
文献类型：
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作者：
Montironi R;Scarpelli M;Lopez-Beltran A;Mazzucchelli R;Alberts D;Ranger-Moore J;Bartels HG;Hamilton PW;Einspahr J;Bartels PH
背景：之前的一项探索性研究(J. Clin。病理学杂志57(2004),1201-1207)表明，对低恶性潜能乳头状尿路上皮肿瘤（PUNLMP）的细胞核进行核学评估，发现表型的细微差异与疾病复发相关。研究目的：在更大的样本量上验证探索性研究的结果。资料：对85例PUNLMP患者的苏木精和伊红染色切片的93个核特征进行分析。45例病例来自孤立性PUNLMP病变患者，在至少8年的随访期间无疾病。另外40例来自单发性PUNLMP患者，随访中有一次或多次复发。将先前定义的分类功能与新的p指数衍生的分类方法相结合，试图对病例进行分类，并确定PUNLMP病变复发的生物标志物。结果：通过多种不同的方法进行验证。首先，探索性研究的确切程序应用于大型验证集。其次，由于探索性研究的判别函数2是基于小样本量的，因此推导了一个新的判别函数。病例分类显示，非复发病例的正确率为61%，复发病例的正确率为74%。通过应用无监督学习技术来利用表型组成（正确分类率为92%），获得了更大的成功。该方法通过将数据分为训练集和测试集来验证，其中2/3的案例分配给训练集，1/3的案例分配给测试集，在旋转的基础上，通过leave-k-out过程在三个独立的数据集上测试分类率的验证。平均正确分类率为92.8%（训练集）和84.6%（测试集）。结论：我们的验证性研究检测了非复发性和复发性PUNLMP之间染色质组织状态的亚视觉差异，从而提供了一种非常稳定的方法来预测低恶性潜能的乳头状尿路上皮肿瘤的复发。
Background: A preceding exploratory study (J. Clin. Pathol. 57(2004), 1201–1207) had shown that a karyometric assessment of nuclei from papillary urothelial neoplasms of low malignant potential (PUNLMP) revealed subtle differences in phenotype which correlated with recurrence of disease. Aim of the Study: To validate the results from the exploratory study on a larger sample size. Materials: 93 karyometric features were analyzed on haematoxylin and eosin-stained sections from 85 cases of PUNLMP. 45 cases were from patients who had a solitary PUNLMP lesion and were disease-free during a follow-up period of at least 8 years. The other 40 were from patients with a unifocal PUNLMP, with one or more recurrences in the follow-up. A combination of the previously defined classification functions together with a new P-index derived classification method was used in an attempt to classify cases and identify a biomarker of recurrence in PUNLMP lesions. Results: Validation was pursued by a number of separate approaches. First, the exact procedure from the exploratory study was applied to the large validation set. Second, since the discriminant function 2 of the exploratory study had been based on a small sample size, a new discriminant function was derived. The case classification showed a correct classification of 61% for non-recurrent and 74% for recurrent cases, respectively. Greater success was obtained by applying unsupervised learning technologies to take advantage of phenotypical composition (correct classification of 92%). This approach was validated by dividing the data into training and test sets with 2/3 of the cases assigned to the training sets, and 1/3 to the test sets, on a rotating basis, and validation of the classification rate was thus tested on three separate data sets by a leave-k-out process. The average correct classification was 92.8% (training set) and 84.6% (test set). Conclusions: Our validation study detected subvisual differences in chromatin organization state between non-recurrent and recurrent PUNLMP, thus allowing a very stable method of predicting recurrence of papillary urothelial neoplasms of low malignant potential by karyometry.