前列腺癌8号染色体改变与Gleason评分之间的相关性

Relationship between chromosome 8 alterations and Gleason score in prostatic adenocarcinoma

目的探索前列腺癌8号染色体数目增加及 c-myc 基因和脂蛋白脂酶(LPL)基因状态和发生频率,分析8号染色体改变与前列腺癌 Gleason 评分之间的相关性及其在前列腺癌发生发展中的作用。方法采用 ProVysion^(TM)三色探针组合,以荧光原位杂交(FISH)方法检测34例未经临床治疗的前列腺癌穿刺组织石蜡切片标本的8号染色体改变,其中包括 Gleason 评分5分者1例,6分者10例,7分者14例,8分者4例,9分者5例,并进行8号染色体各种异常之间及其与前列腺癌 Gleason评分级别之间的关联性分析。结果 8号染色体增加为17/34(50%),c-myc 基因拷贝数增加为21/34(61.8%),LPL 单体为15/34(44.1%),c-myc 基因扩增为23/34(67.6%),LPL 基因缺失为21/34(61.8%),同时具有 LPL 基因缺失和 c-myc 基因扩增为16/34(47.1%),至少有其中一种遗传学异常者为29/34(85.3%)。8号染色体增加与 Gleason 评分级别增高呈明显的正相关关系(P=0.0006);c-myc 基因拷贝数增加与 Gleason 评分级别增高呈正相关关系(P=0.0035);LPL 缺失与 Gleason 评分级别增高呈负相关关系(P=0.0383);调整年龄后,除了上述三个变量与 Gleason 评分级别的相关关系仍然存在以外,c-myc 基因扩增与 Gleason 评分级别增高也呈现正相关关系(P=0.0462)。结论 8号染色体数目增加、c-myc 基因拷贝数增加、c-myc 基因扩增和 LPL 基因丢失都与 Gleason 评分级别有关,c-myc 基因扩增同时伴有 LPL 基因缺失也是前列腺癌的遗传学特征之一,提示8号染色体异常可能与前列腺癌的发生和进展有关。

Objective To study the gain of chromosome 8 and c-myc gene and lipoprotein lipase gene status in prostatic adenocarcinoma of Chinese patients, and to analyze the relationship between chromosome 8 alterations and Gleason score of prostatic cancer. Methods Formalin-fixed, paraffinembedded prostatic biopsy tissues from 34 Chinese patients with untreated prostatic adenocarcinoma were studied by three-color fluorescence in situ hybridization （ FISH ） using ProVysionTM probe kit. The materials included 1 case with Gleason score 5, 10 cases with Gleason score 6, 14 cases with Gleason score 7, 4 cases with Gleason score 8 and 5 cases with Gleason score 9. The relationship between Gleason score and chromosome 8 aneusomy, c-myc and lipoprotein lipase gene copy number, including gene amplification or deletion, were analyzed. Results Seventeen （50%） of the 34 cases studied had gain of chromosome 8, while 21 cases （61.8%） had gain of c-myc gene copy number, 15 cases （44. 1% ） had lipoprotein lipase gene monosomy, 23 cases （67.6%） had c-myc gene amplification, 21 cases （61.8%） had deletion of lipoprotein lipase gene and 16 cases （47. 1% ） had lipoprotein lipase gene deletion coupled with c-myc gene amplification. In general, at least one type of chromosome 8 alteration was identified in 85.3% of cases （29/34）. Gain of chromosome 8 was strong significant associated with Gleason score （P = 0. 0006 ）. A positive correlation between increased c-myc copy number and high Gleason score was also noted （ P = 0. 0035 ）. On the other hand, loss of lipoprotein lipase gene was negatively correlated with high Gleason score （P = 0. 0383 ）. In addition, the association of c-myc gene amplification with high Gleason score was noted after age adjustment （P = 0. 0462 ）. Conclusions Alterations in chromosome 8 are common in prostatic adenocarcinoma occurring in Chinese patients. There is a correlation between Gleason score and gain of chromosome 8, increased c-myc gene copy number, c-myc gene amplification and lipoprotein lipase gene deletion. C-myc gene amplification accompanied by lipoprotein lipase gene deletion is also a common occurrence in prostatic cancer. Our data suggest that chromosome 8 alterations may play some roles in the development and progression of prostatic adenocarcinoma.