Lu Wei, Takahashi Hiroyuki, Furusato Bungo, Maekawa Suguru, Ikegami Masahiro, Sudo Akemi, Egawa Shin, Hano Hiroshi
Department of Pathology, Jikei University School of Medicine, Nishishimbashi, Tokyo, Japan.
Genes Chromosomes Cancer. 2006 May;45(5):509-15. doi: 10.1002/gcc.20314.
In this study, we used 7 informative microsatellite markers at 8p22, 23.1, and 23.2 in Japanese patients to compare frequency of loss of heterozygosity (LOH) in 53 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC), 31 cases (41 lesions) of latent prostate cancer (LPC), and 102 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 8p22-23.2 with at least 1 marker was 0%, 33%, 57%, and 51% in the HGPIN, IPC, LPC, and CPC cases, respectively. No statistically significant difference was found at 8p22-23.2 between the types of prostate cancer. However, the frequency of 8p22 deletion was significantly higher in CPC and LPC cases than in IPC cases (P = 0.0003) or lesions (P = 0.0017). The frequency of LOH at 8p22 and 8p23.1 loci in high-grade tumors was significantly higher than in low-grade tumors in both the LPCs/IPCs and CPCs (P < 0.05). Allelic loss at 8p22 was significantly more frequent in CPC than in IPC (P = 0.002) and in pT4 CPC than in earlier-stage CPC (P = 0.038). These findings suggest that deletion of 8p is an important event in both the initiation and metastasis of prostate cancer. The extremely high frequency of LOH at 8p22-23.1 in high-grade tumors suggests the existence of a novel putative tumor-suppressor gene associated with the progression of prostate cancer. These results should be useful in identifying the target gene of deletion at 8p.
在本研究中,我们对日本患者使用位于8p22、23.1和23.2的7个信息性微卫星标记,以比较53个高级别前列腺上皮内瘤变(HGPIN)病灶、38例(38个病灶)偶发性前列腺癌(IPC)、31例(41个病灶)潜伏性前列腺癌(LPC)和102例(168个病灶)临床前列腺癌(CPC)中杂合性缺失(LOH)的频率。在HGPIN、IPC、LPC和CPC病例中,至少有1个标记的8p22 - 23.2处LOH频率分别为0%、33%、57%和51%。在前列腺癌类型之间,8p22 - 23.2处未发现统计学上的显著差异。然而,CPC和LPC病例中8p22缺失的频率显著高于IPC病例(P = 0.0003)或病灶(P = 0.0017)。在LPC/IPC和CPC中,高级别肿瘤中8p22和8p23.1位点的LOH频率显著高于低级别肿瘤(P < 0.05)。CPC中8p22处的等位基因缺失显著比IPC中更频繁(P = 0.002),且pT4 CPC中比早期CPC中更频繁(P = 0.038)。这些发现表明8p缺失是前列腺癌发生和转移中的一个重要事件。高级别肿瘤中8p22 - 23.1处极高的LOH频率表明存在一个与前列腺癌进展相关的新型假定肿瘤抑制基因。这些结果对于鉴定8p缺失的靶基因应是有用的。