Tollenaar R A, Bonsing B A, Kuipers-Dijkshoorn N J, Hermans J, van de Velde C J, Cornelisse C J, Fleuren G J
Department of Surgery, Leiden University Medical Centre, The Netherlands.
Cancer. 1997 Apr 1;79(7):1304-14.
The aim of this study was to investigate the generation of DNA ploidy diversity in different stages of colorectal carcinoma development.
DNA flow cytometry was performed on tissue samples from 20 colorectal adenomas, 38 colorectal carcinomas, 30 lymph node metastases, and 70 hematogenous metastases.
DNA aneuploidy was detected in 30% of the adenomas, 82% of the primary colorectal tumors, 57% of the lymph node metastases, 92% of the liver metastases, and 100% of the other distant hematogenous metastases. Multiple DNA tumor stemlines were found in 10%, 39%, 29%, 24%, and 40%, respectively. Sixty-two percent of the DNA tumor stemlines detected in the lymph node or liver metastases were also present in the primary tumors. In primary carcinomas and lymph node metastases, the DNA index distribution had a bimodal shape with a minimum at the 1.2-1.4 region. In the hematogenous metastases, a higher percentage of hypertetraploid stemlines was found.
The emergence of DNA aneuploidy as well as clonal divergence seems to take place during the transition from adenoma to carcinoma. The DNA aneuploid stemlines formed during this phase remain relatively stable over time, although ongoing clonal evolution at distant metastatic tumor sites cannot be completely ruled out.
本研究旨在调查结直肠癌发展不同阶段DNA倍体多样性的产生情况。
对20例结直肠腺瘤、38例结直肠癌、30例淋巴结转移灶及70例血行转移灶的组织样本进行DNA流式细胞术检测。
在30%的腺瘤、82%的原发性结直肠癌、57%的淋巴结转移灶、92%的肝转移灶及100%的其他远处血行转移灶中检测到DNA非整倍体。分别在10%、39%、29%、24%和40%的样本中发现多个DNA肿瘤干细胞系。在淋巴结或肝转移灶中检测到的DNA肿瘤干细胞系，62%也存在于原发性肿瘤中。在原发性癌和淋巴结转移灶中，DNA指数分布呈双峰状，在1.2 - 1.4区域出现最小值。在血行转移灶中，发现更高比例的超四倍体干细胞系。
DNA非整倍体的出现以及克隆分歧似乎发生在从腺瘤向癌转变的过程中。尽管不能完全排除远处转移肿瘤部位持续的克隆进化，但在此阶段形成的DNA非整倍体干细胞系随时间推移保持相对稳定。
