Palmeira C, Oliveira P A, Arantes-Rodrigues R, Colaço A, De la Cruz P L F, Lopes C, Santos L
Department of Immunology, Portuguese Institute of Oncology, 4200-072 Porto, Portugal.
Oncol Rep. 2009 Jan;21(1):247-52.
The aims of this study were to evaluate the DNA content of chemically-induced rat urothelial lesions and their relationship to the proliferation index and histological patterns. Sixty female Fisher 344 rats were divided randomly into six groups, four groups were exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine for a period of 10 and 20 weeks, and two groups of ten rats were used as control animals. Paraffin sections were Feulgen stained and analyzed using DNA image cytometry analysis; histograms were classified as either diploid or aneuploid. Ki-67 immunoreactivity was determined by means of the streptavidin-biotin-complex immunoperoxidase method. All normal urothelium from the control groups were found to have diploid DNA content. The same histogram pattern was found in the simple hyperplasia group. As regards the other histological lesions, the frequency of the aneuploidy varied depending on the lesion type: 20% of aneuploidy were nodular hyperplasia, 32% of aneuploidy were dysplasias, 25% of aneuploidy were papilloma, 44% of aneuploidy were papillary neoplasm of low malignant potential, 22% of aneuploidy were low-grade papillary carcinoma, 100% of aneuploidy were high-grade papillary carcinoma and 100% of the aneuploidy were invasive carcinoma. Our results revealed the existence of a statistically significant relationship between DNA ploidy and histological pattern lesions (r=0.3, p<0.023). The Ki-67 proliferation index was significantly higher in aneuploid lesions than in diploid (r=0.56, p=0.01). There was also a statistically significant difference in the Ki-67 proliferation index in relation to the histopathological pattern (r=0.751, p<0.01). DNA content was associated with the Ki-67 proliferation index and histopathological grade. DNA content and prolife-ration index have critical roles to play during urothelial carcinogenesis.
本研究的目的是评估化学诱导的大鼠膀胱上皮病变的DNA含量及其与增殖指数和组织学模式的关系。60只雌性Fisher 344大鼠被随机分为6组，4组暴露于N-丁基-N-(4-羟基丁基)亚硝胺10周和20周，两组各10只大鼠作为对照动物。石蜡切片进行Feulgen染色，并使用DNA图像细胞术分析；直方图分为二倍体或非整倍体。通过链霉亲和素-生物素复合物免疫过氧化物酶法测定Ki-67免疫反应性。对照组所有正常膀胱上皮均为二倍体DNA含量。单纯增生组也发现相同的直方图模式。至于其他组织学病变，非整倍体的频率因病变类型而异：20%的非整倍体为结节状增生，32%为发育异常，25%为乳头状瘤，44%为低恶性潜能乳头状肿瘤，22%为低级别乳头状癌，100%为高级别乳头状癌，100%为浸润性癌。我们的数据显示DNA倍性与组织学模式病变之间存在统计学上的显著关系（r=0.3，p<0.023）。非整倍体病变中的Ki-67增殖指数显著高于二倍体病变（r=0.56，p=0.01）。Ki-67增殖指数在组织病理学模式方面也存在统计学上的显著差异（r=0.751，p<0.01）。DNA含量与Ki-67增殖指数和组织病理学分级相关。DNA含量和增殖指数在膀胱上皮癌发生过程中起着关键作用。
