Alers J C, Krijtenburg P J, Vissers C J, Bosman F T, van der Kwast T H, van Dekken H
Department of Pathology, Erasmus University Rotterdam, The Netherlands.
Cytometry. 1995 Sep 1;21(1):84-94. doi: 10.1002/cyto.990210116.
Twenty-five prostatic adenocarcinomas were studied for the presence of intratumoral cytogenetic heterogeneity by interphase in situ hybridization (ISH) to routinely processed tissue sections. ISH with a chromosome Y-specific repetitive DNA probe provided a model to investigate patterns of chromosomal heterogeneity within and between different pathological grades. The Gleason grading system was used, since it is based on a detailed classification of growth patterns. Heterogeneity with respect to ploidy of the tumor was examined by ISH with a repetitive DNA probe specific for chromosome 1. The ploidy status of these cancers was confirmed by DNA flow cytometry (P < 0.001). Cytogenetic heterogeneity at the (Y) chromosomal level was observed between Gleason areas, within one area, and even within single tumor glands. The different patterns of chromosomal heterogeneity were seen in all tumor grades and stages. Differences in ploidy status were also found following the aforementioned histological patterns, again, in all grades and stages. Intraglandular heterogeneity was most frequently seen. No correlation was found between cytogenetic heterogeneity and proliferative activity (Ki-67 immunostaining). In contrast to current views on clonality, suggesting regional separation of subclones with different DNA content, this study demonstrates that these subclones can be interspersed.
通过对常规处理的组织切片进行间期原位杂交（ISH），研究了25例前列腺腺癌肿瘤内细胞遗传学异质性的存在情况。使用染色体Y特异性重复DNA探针进行ISH，为研究不同病理分级内和不同病理分级之间的染色体异质性模式提供了一个模型。采用Gleason分级系统，因为它基于生长模式的详细分类。通过使用针对染色体1的重复DNA探针进行ISH，检测肿瘤倍体的异质性。这些癌症的倍体状态通过DNA流式细胞术得到证实（P < 0.001）。在Gleason区域之间、一个区域内甚至单个肿瘤腺体内均观察到（Y）染色体水平的细胞遗传学异质性。在所有肿瘤分级和分期中均可见不同的染色体异质性模式。同样，在所有分级和分期中，按照上述组织学模式也发现了倍体状态的差异。腺体内异质性最为常见。未发现细胞遗传学异质性与增殖活性（Ki-67免疫染色）之间存在相关性。与目前关于克隆性的观点相反，即认为具有不同DNA含量的亚克隆是区域分离的，本研究表明这些亚克隆可以相互穿插。
