Russo A, Migliavacca M, Bazan V, Maturi N, Morello V, Dardanoni G, Modica G, Bazan P, Albanese I, La Farina M, Tomasino R M
Department of Clinical Oncology Research, University of Palermo, Italy.
Cell Prolif. 1998 Jun-Aug;31(3-4):139-53. doi: 10.1046/j.1365-2184.1998.00116.x.
Paired colorectal liver metastases (CLM) and normal tissue samples from a consecutive series of 36 patients were studied prospectively. MIB-1 expression was studied by immunohistochemistry on paraffin-embedded sections. DNA ploidy and S-phase fraction (SPF) measurements were performed by flow cytometry on frozen tissues. Mutations within the p53 (exons 5-8) and c-Ki-ras (codons 12 and 13) genes were detected by PCR single-strand conformation polymorphism analysis followed by sequencing. A high correlation was observed between the MIB-1 LI and SPF value (rho=0.81; P<0.01). Moreover, p53 gene mutations were associated with either high MIB-1 LI and high SPF. In univariate analysis, SPF and MIB-1 levels were related to risk of death. The association between overall survival and DNA-ploidy or p53 mutations did not reach statistical significance, but a slightly better survival was observed for patients either with DNA-diploid tumours or without mutations (P=0.05 and P=0.06, respectively). SPF was shown by multivariate Cox model analysis to be an independent prognostic variable and thus it might be a useful prognostic factor in patients with CLM.
对连续36例患者的配对结直肠癌肝转移灶（CLM）和正常组织样本进行了前瞻性研究。通过免疫组织化学法在石蜡包埋切片上研究MIB-1表达。通过流式细胞术对冷冻组织进行DNA倍体和S期分数（SPF）测量。通过PCR单链构象多态性分析及测序检测p53基因（外显子5 - 8）和c-Ki-ras基因（密码子12和13）内的突变。观察到MIB-1标记指数（LI）与SPF值之间高度相关（rho = 0.81；P < 0.01）。此外，p53基因突变与高MIB-1 LI和高SPF相关。单因素分析中，SPF和MIB-1水平与死亡风险相关。总生存期与DNA倍体或p53突变之间的关联未达到统计学意义，但DNA二倍体肿瘤患者或无突变患者的生存期稍好（分别为P = 0.05和P = 0.06）。多因素Cox模型分析显示SPF是一个独立的预后变量，因此它可能是CLM患者有用的预后因素。
