散发性结直肠癌的染色体不稳定研究及其临床病理意义

目的 探讨散发性结直肠癌（sporadic colorectal cancer,SCRC）的DNA倍体异常和染色体畸变的数目、部位及其与临床病理特征之间的关系.方法 将40例SCRC肿瘤标本制备成单细胞悬液,经染色后进行流式细胞术（flow cytometry,FCM）检测,分析肿瘤细胞DNA倍体;采用比较基因组杂交技术（comparative genomic hybridization,CGH）在全基因组水平对40例SCRC进行染色体畸变检测.结果 40例SCRC患者标本中,二倍体的比例为42.5%,异倍体为57.5%,DNA倍体与TNM分期有密切关系,分期越高,异倍体的比例越高,差异有统计学意义（P＜0.05）.CGH检测的所有病例均有不同程度的染色体畸变,平均每例畸变数为7.55,常见的染色体扩增区域有：20q、12q、13q、7p等,常见缺失区域有18q、5q、4q、8p等.TNM分期中Ⅲ～Ⅳ期SCRC的染色体畸变数高于Ⅰ～Ⅱ期（6.00±2.76 vs 8.70±2.84,P＜0.05）.不同肿瘤部位、分化程度、组织学类型SCRC的DNA倍体差异无统计学意义（P ＞0.05）.二倍体肿瘤的染色体畸变数明显少于异倍体肿瘤（6.35±3.35 vs 8.43±2.59,P＜0.05）.结论 染色体不稳定在SCRC中普遍存在,是SCRC病情进展的基础,染色体畸变比DNA倍体异常更为常见.

Correlation of chromosome instability with clinicopathological features of sporadic colorectal cancer

Objective To investigate the DNA ploidy and chromosomal aberration and their relationship with clinicopathological features of sporadic colorectal cancer （SCRC）. Methods The DNA ptoidy was evaluated by flow cytometry （FCM） and the chromosomal aberration was detected by comparative genomic hybridization （CGH） in tissue samples from 40 patients with sporadic colorectal cancer. Results The rates of diploidy and aneuploidy in 40 SCRC samples were 42.5% and 57.5% respectively. DNA ploidy was correlated with tumor TNM stages and the association between aneuploidy and advanced stages of the disease was statistically significant. We found chromosome frequent gains at 20q, 12q, 13q, 7p, while loss was often noted at 18q, 5q, 4q, 8p. The number of chromosomal aberration in TNM Ⅲ-Ⅳ was higher than that in TNM Ⅰ-Ⅱ tumor （8.43 ± 2.59 vs 6.35 ±3.35, P〈 0.05）. No significant association was found between the number of chromosomal aberration and tumor site, histopathological type and histological grade. In aneuploidy tumor, there were significantly more gains and losses of chromosomal aberrations than in diploidy tumors. Conclusion Chromosome instability exists in sporadic colorectal carcinoma and chromosomal aberration is more common than DNA heteroploidy.