Alers J C, Krijtenburg P J, Vis A N, Hoedemaeker R F, Wildhagen M F, Hop W C, van Der Kwast T T, Schröder F H, Tanke H J, van Dekken H
Department of Pathology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Am J Pathol. 2001 Feb;158(2):399-406. doi: 10.1016/s0002-9440(10)63983-1.
No objective parameters have been found so far that can predict the biological behavior of early stages of prostatic cancer, which are encountered frequently nowadays due to surveillance and screening programs. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded radical prostatectomy specimens derived from patients who participated in the European Randomized Study of Screening for Prostate Cancer. We defined a panel consisting of 36 early cancer specimens: 13 small (total tumor volume (Tv) < 0.5 ml) carcinomas and 23 intermediate (Tv between 0.5-1.0 ml) tumors. These samples were compared with a set of 16 locally advanced, large (Tv > 2.0 ml) tumor samples, not derived from the European Randomized Study of Screening for Prostate Cancer. Chromosome arms that frequently (ie, > or = 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, > or = 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). No consistent gains were found in this group. In the large tumors, loss was seen of 13q (69%), 8p (50%), 5q, 6q (both 31%), and Y (15%). Gains were observed of 8q (37%), 3q (25%), 7p, 7q, 9q, and Xq (all 19%). Comparison of these early, localized tumors with large adenocarcinomas showed a significant increase in the number of aberrant chromosomes per case (Rs = 0.36, P = 0.009). The same was true for the number of lost or gained chromosomes per case (Rs = 0.27, P: = 0.05; Rs = 0.48, respectively; P < 0.001). Interestingly, chromosomal alterations that were found in previous studies to be potential biomarkers for tumor aggressiveness, ie, gain of 7pq and/or 8q, were already distinguished in the small and intermediate cancers. In conclusion, our data show that chromosomal losses, more specifically of 6q and 13q, are early events in prostatic tumorigenesis, whereas chromosomal gains, especially of 8q, appear to be late events in prostatic tumor development. Finally, early localized tumors, as detected by screening programs, harbor cancers with aggressive genetic characteristics.
目前尚未发现能够预测前列腺癌早期生物学行为的客观参数，由于监测和筛查项目，如今前列腺癌早期病例屡见不鲜。我们将比较基因组杂交技术应用于常规处理的、石蜡包埋的根治性前列腺切除术标本，这些标本来自参与欧洲前列腺癌筛查随机研究的患者。我们定义了一个由36个早期癌症标本组成的样本组：13个小肿瘤（肿瘤总体积（Tv）<0.5 ml）和23个中等大小肿瘤（Tv在0.5 - 1.0 ml之间）。这些样本与一组16个局部晚期大肿瘤（Tv>2.0 ml）样本进行比较，后者并非来自欧洲前列腺癌筛查随机研究。在小肿瘤中频繁（即≥15%）出现缺失的染色体臂包括13q（31%）、6q（23%）和Y（15%），而频繁（即≥15%）出现增益的是20q（15%）。在中等大小癌症中，检测到8p（35%）、16q（30%）、5q（26%）、Y（22%）、6q和18q（均为17%）缺失。该组未发现一致的增益情况。在大肿瘤中，可见13q（69%）、8p（50%）、5q、6q（均为31%）和Y（15%）缺失。观察到8q（37%）、3q（25%）、7p、7q、9q和Xq（均为19%）增益。将这些早期局限性肿瘤与大腺癌进行比较，发现每例异常染色体数量显著增加（Rs = 0.36，P = 0.009）。每例丢失或增益染色体的数量情况相同（Rs分别为0.27，P = 0.05；Rs = 0.48，P < 0.001）。有趣的是，先前研究中发现的作为肿瘤侵袭性潜在生物标志物的染色体改变，即7pq和/或8q增益，在小肿瘤和中等大小癌症中已可区分。总之，我们的数据表明，染色体缺失，尤其是6q和13q缺失，是前列腺肿瘤发生的早期事件，而染色体增益，特别是8q增益，似乎是前列腺肿瘤发展的晚期事件。最后，筛查项目检测到的早期局限性肿瘤所携带的癌症具有侵袭性遗传特征。
