Sato Hirotaka, Minei Sadatsugu, Hachiya Takahiko, Yoshida Toshio, Takimoto Yukie
Departments of Urology, Nihon University School of Medicine, Tokyo, Japan.
Int J Urol. 2006 Jun;13(6):761-6. doi: 10.1111/j.1442-2042.2006.01399.x.
Genetic aberration such as the amplification of c-myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c-myc gene), related to the progression and survival in advanced (Stage C) prostate cancer.
We used dual-probe fluorescence in situ hybridization with a centromere-specific probe for chromosome 8 (8cen), and with a region-specific probe for c-myc (8q24) to evaluate genetic changes in tumor samples from 50 patients who had undergone radical retropubic prostatectomy from 1986 to 2001.
We classified the 8cen and c-myc copy numbers as normal, gain and amplification. The carcinoma foci with extra copies of c-myc, which was defined in 35 cases (70%), were divided into two groups: (a) a simple gain of the whole chromosome 8 (no increase in the c-myc copy number relative to the chromosome 8 centromere), which was identified in 15 cases (30%); and (b) a substantial amplification of c-myc (additional increases [AI] in the c-myc copy number relative to the chromosome 8 centromere), which was detected in 20 cases (40%). AI-c-myc was strongly associated with higher histopathological grades and Gleason's scores (P = 0.0330, 0.0190, respectively). Patients with the AI-c-myc had earlier disease progression (P = 0.0029) and earlier cancer death (P = 0.0087) than did patients with normal patterns.
Identification of an AI-c-myc may serve as a potential marker of prostate cancer progression.
基因畸变如c-myc扩增在晚期前列腺癌中普遍存在。本研究旨在阐明8号染色体改变,包括8q24(c-myc基因)的获得和扩增,与晚期(C期)前列腺癌的进展和生存的关系。
我们使用了一种针对8号染色体的着丝粒特异性探针(8cen)和一种针对c-myc的区域特异性探针(8q24)的双探针荧光原位杂交技术,来评估1986年至2001年间接受耻骨后根治性前列腺切除术的50例患者肿瘤样本中的基因变化。
我们将8cen和c-myc的拷贝数分为正常、获得和扩增。35例(70%)定义为具有额外c-myc拷贝的癌灶被分为两组:(a)整个8号染色体的单纯获得(相对于8号染色体着丝粒,c-myc拷贝数无增加),15例(30%)被鉴定为此类;(b)c-myc的大量扩增(相对于8号染色体着丝粒,c-myc拷贝数额外增加[AI]),20例(40%)检测到此类。AI-c-myc与更高的组织病理学分级和Gleason评分密切相关(分别为P = 0.0330,0.0190)。与具有正常模式的患者相比,AI-c-myc患者疾病进展更早(P = 0.0029),癌症死亡更早(P = 0.0087)。
鉴定出AI-c-myc可能作为前列腺癌进展的潜在标志物。