Tagawa Y, Yasutake T, Sawai T, Nanashima A, Jibiki M, Morinaga M, Akama F, Nakagoe T, Ayabe H
The First Department of Surgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852, Japan.
Clin Cancer Res. 1997 Sep;3(9):1587-92.
Numerical chromosome aberrations by interphase cytogenetic analysis have been reported in a few samples of colorectal neoplasms. No studies have defined a distinct relationship between these aberrations and clinicopathological features. To investigate the chromosome aberrations as a marker of invasiveness or prognosis, we conducted an interphase cytogenetic study using fluorescence in situ hybridization and examined 142 colorectal neoplasms consisting of 15 adenomas and 127 cancers. The target chromosomes were chromosomes 11 and 17. We also evaluated the nuclear DNA content as detected by flow cytometry, analyzed the relationship between the frequency of aneusomy and clinicopathological features, and examined the survival rate in these patients. The loss of chromosome 11 was observed in 31% of adenomas, whereas in cancers DNA aneuploidy was observed in 63% of cases, a gain of chromosome 17 was observed in 63% of cases, and a gain of chromosome 11 was observed in 42% of cases. Numerical chromosome aberrations in diploid DNA were also observed. Increased depth of invasion (>/=T3) and advanced Dukes' stage (>/=B) of malignant tumors were associated with a higher frequency of a gain of chromosome 11 (P < 0.01 and P < 0.05, respectively). Increased depth of invasion (>/=T2) in cancers was associated with a higher frequency of a gain of chromosome 17 (P < 0.05). Multivariate analysis of postoperative survival showed that a loss or gain of chromosome 11 was independently associated with a poor prognosis (P < 0.05). Numerical chromosome aberrations appear prior to the alteration of nuclear DNA content as detected by flow cytometry and influence the progression of colorectal cancers. Aneusomy of chromosome 11 is associated with poor postoperative prognosis of primary colorectal cancers.
通过间期细胞遗传学分析,在少数结直肠肿瘤样本中已报道存在染色体数目异常。尚无研究明确这些异常与临床病理特征之间的独特关系。为了研究染色体异常作为侵袭性或预后标志物,我们使用荧光原位杂交进行了一项间期细胞遗传学研究,并检查了142例结直肠肿瘤,其中包括15例腺瘤和127例癌。靶染色体为11号和17号染色体。我们还通过流式细胞术评估了核DNA含量,分析了非整倍体频率与临床病理特征之间的关系,并检查了这些患者的生存率。在31%的腺瘤中观察到11号染色体缺失,而在癌中,63%的病例观察到DNA非整倍体,63%的病例观察到17号染色体增加,42%的病例观察到11号染色体增加。在二倍体DNA中也观察到染色体数目异常。恶性肿瘤浸润深度增加(≥T3)和Dukes分期进展(≥B)与11号染色体增加的频率较高相关(分别为P<0.01和P<0.05)。癌浸润深度增加(≥T2)与17号染色体增加的频率较高相关(P<0.05)。术后生存的多因素分析表明,11号染色体的缺失或增加与预后不良独立相关(P<0.05)。染色体数目异常在通过流式细胞术检测到的核DNA含量改变之前出现,并影响结直肠癌的进展。11号染色体非整倍体与原发性结直肠癌术后预后不良相关。