Soder A I, Hopman A H, Ramaekers F C, Conradt C, Bosch F X
Molecular Biology Laboratory, Ear, Nose, and Throat University Hospital, University of Heidelberg, Germany.
Cancer Res. 1995 Nov 1;55(21):5030-7.
Fifty-one randomly selected primary squamous cell carcinomas of the head and neck, derived from the larynx (n = 18) and pharynx (oropharynx, n = 18, and hypopharynx, n = 15) were analyzed with centromeric probes for chromosomes 1, 7, 9, 11, 17, and 18 to study numerical aberrations, chromosome imbalances, and aneuploidy by fluorescence in situ hybridization. The tumors were grouped into nonmetastasizing (N0) tumors (from patients clinically free of lymph node metastases for at least 18 months after surgery, n = 25) and metastasizing (N1-3) tumors (n = 26). We found a significant association between the tumor ploidy and the nodal status; in the N0 group, diploidy prevailed, and the most common aberration was loss to monosomy for chromosome 9 (44%), whereas in the N1-3 group, aneuploidy predominated (P = 0.002). Specifically, these genomic changes associated with progression to metastasis were: (a) tetrasomic or polysomic chromosomes were detected in 17 of 26 N1-3 tumors but in none of the 25 N0 tumors (P < 0.0001); (b) heterogeneous chromosomal copy numbers (i.e., extensive chromosomal imbalances) were also much more frequent in the N1-3 tumors (69.2% versus 24.0% in the N0 group; P = 0.018); and (c) loss of chromosome 9 (73%) and gains of chromosomes 7 (35%) and 17 (31%) persisted, but in addition, loss of chromosome 18 occurred in 31%. Overexpression of the p53 protein correlated with an increased incidence of chromosomal imbalances and aneuploidy (P < 0.001) and, hence, constituted an additional risk factor. The lower metastatic potential of larynx tumors as compared with tumors from the pharynx was reflected by a lower incidence of these genomic changes. These specific patterns of chromosomal aberrations can characterize and distinguish different stages of tumor progression of squamous cell carcinomas of the head and neck and should be valuable diagnostic and prognostic markers.
选取51例随机挑选的头颈部原发性鳞状细胞癌，这些肿瘤来源于喉（n = 18）和咽（口咽，n = 18，下咽，n = 15），使用针对1、7、9、11、17和18号染色体的着丝粒探针进行分析，通过荧光原位杂交研究数值畸变、染色体失衡和非整倍体情况。将肿瘤分为无转移（N0）肿瘤（来自术后临床无淋巴结转移至少18个月的患者，n = 25）和有转移（N1 - 3）肿瘤（n = 26）。我们发现肿瘤倍性与淋巴结状态之间存在显著关联；在N0组中，二倍体占主导，最常见的畸变是9号染色体单体性缺失（44%），而在N1 - 3组中，非整倍体占主导（P = 0.002）。具体而言，与转移进展相关的这些基因组变化包括：（a）在26例N1 - 3肿瘤中有17例检测到四体或多体染色体，但25例N0肿瘤中均未检测到（P < 0.0001）；（b）异质性染色体拷贝数（即广泛的染色体失衡）在N1 - 3肿瘤中也更为常见（N0组为24.0%，N1 - 3组为69.2%；P = 0.018）；（c）9号染色体缺失（73%）以及7号（35%）和17号（31%）染色体增加仍然存在，但此外，18号染色体缺失发生在31%。p53蛋白的过表达与染色体失衡和非整倍体发生率增加相关（P < 0.001），因此构成了一个额外的风险因素。与咽肿瘤相比，喉肿瘤较低的转移潜能体现在这些基因组变化的发生率较低。这些特定的染色体畸变模式可以表征和区分头颈部鳞状细胞癌肿瘤进展的不同阶段，应该是有价值的诊断和预后标志物。
