Garcia Jacinto, Duran Angel, Tabernero Maria Dolores, Garcia Plaza Asunción, Flores Corral Teresa, Najera Maria Luisa, Gomez-Alonso Alberto, Orfao Alberto
Servicio de Cirugia, Hospital Universitario and Departamento de Cirugia, Centro de Investigaciones del Cancer, Universidad de Salamanca, Salamanca, Spain.
Cytometry B Clin Cytom. 2003 Jan;51(1):14-20. doi: 10.1002/cyto.b.10006.
In recent years important information has accumulated on the genetic alterations present in colorectal tumors. However, thus far few studies have analyzed the impact of numerical abnormalities of chromosomes 17 and 18, which carry the p53 and DCC plus SHAD4/DPC4 genes involved in colorectal cancer, on the clinical and biological behaviors of the disease.
With the use of interphase fluorescence in situ hybridization (FISH), we analyzed the incidence of numerical abnormalities of chromosomes 17 and 18 in a series of malignant colorectal tumors and explored its potential association with clinicobiological behavior and the prognosis of the disease. For this purpose, 94 consecutive patients newly diagnosed with colorectal cancer were analyzed. In all cases, FISH analyses of the number of copies and nuclei of chromosomes 17 and 18 were performed in interphase nuclei with the use of double stainings. For all patients, information on age, sex, tumor size, Dukes' stage, tumor localization, DNA ploidy status, and the proportion of S-phase tumor cells was recorded. Median follow-up was 38 months.
Numerical abnormalities of chromosomes 17 and 18 were present in most patients with colorectal cancer (57% and 52%, respectively). Gains of chromosome 17 and monosomy 18 were found in 51% and 29% of cases, respectively, and they were the most frequent individual abnormalities for each chromosome. The simultaneous analysis of the number of copies of both chromosomes in the same cell showed that, in most cases displaying numerical abnormalities for these chromosomes, two or more different tumor cell clones were present. From a clinical point of view, numerical abnormalities of chromosome 17, especially monosomy 17, were associated with a significantly higher incidence of rectal tumors (P = 0.001) and Dukes' stage D (P = 0.02) and a lower median of disease-free survival among patients who underwent curative surgery (P = 0.05), as compared with diploid cases. In addition, cases with an altered number of copies of chromosome 17 showed a higher incidence of DNA aneuploidy (P = 0.0001) and a greater proportion of S-phase cells (P = 0.001) by flow cytometry. In contrast, no clear association was found between the presence of numerical abnormalities of chromosome 18 and clinicobiological disease characteristics, except for a higher incidence of DNA aneuploidy by flow cytometry (P = 0.001) and a lower median of disease-free survival (P = 0.06). Multivariate analysis showed that numerical abnormalities of chromosome 17, but not of chromosome 18, are an independent prognostic factor for predicting disease-free survival in patients with colorectal cancer.
Numerical abnormalities of chromosomes 17 and 18 were relatively common findings in patients with colorectal cancer, with chromosome 17 being associated with a higher incidence of tumors localized to the rectum and a worse clinical outcome. Cytometry Part B (Clin. Cytometry) 51B:14-20, 2003.
近年来，有关结肠直肠肿瘤中存在的基因改变的重要信息不断积累。然而，迄今为止，很少有研究分析携带与结直肠癌相关的p53和DCC加SHAD4/DPC4基因的17号和18号染色体数目异常对该疾病临床和生物学行为的影响。
我们采用间期荧光原位杂交（FISH）技术，分析了一系列恶性结肠直肠肿瘤中17号和18号染色体数目异常的发生率，并探讨其与临床生物学行为及疾病预后的潜在关联。为此，对94例新诊断为结肠癌的连续患者进行了分析。所有病例均使用双色染色法在间期核中对17号和18号染色体的拷贝数和细胞核进行FISH分析。记录了所有患者的年龄、性别、肿瘤大小、Dukes分期、肿瘤定位、DNA倍体状态以及S期肿瘤细胞比例。中位随访时间为38个月。
大多数结肠癌患者存在17号和18号染色体数目异常（分别为57%和52%）。17号染色体增益和18号染色体单体分别在51%和29%的病例中发现，它们是每条染色体最常见的个体异常。对同一细胞中两条染色体拷贝数的同时分析表明，在大多数显示这些染色体数目异常的病例中，存在两个或更多不同的肿瘤细胞克隆。从临床角度来看，与二倍体病例相比，17号染色体数目异常，尤其是17号染色体单体，与直肠肿瘤的发生率显著更高（P = 0.001）、Dukes分期D（P = 0.02）以及接受根治性手术患者的无病生存期中位数更低（P = 0.05）相关。此外，17号染色体拷贝数改变的病例通过流式细胞术显示DNA非整倍体发生率更高（P = 0.0001）和S期细胞比例更大（P = 0.001）。相比之下，除了通过流式细胞术显示DNA非整倍体发生率更高（P = 0.001）和无病生存期中位数更低（P = 0.06）外，未发现18号染色体数目异常与临床生物学疾病特征之间存在明确关联。多变量分析表明17号染色体而非18号染色体数目异常是预测结肠癌患者无病生存期的独立预后因素。
17号和18号染色体数目异常在结肠癌患者中是相对常见的发现，17号染色体与直肠肿瘤发生率更高及临床结局更差相关。《细胞分析B辑（临床细胞分析）》51B:14 - 20, 2003年
