Caamano J, Zhang S Y, Rosvold E A, Bauer B, Klein-Szanto A J
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Am J Pathol. 1993 Apr;142(4):1131-9.
p53 alterations were studied in a group of 22 primary squamous cell carcinomas (SCC) of the head and neck and in 10 cell lines derived from SCC. Positive immunohistochemical detection of p53 was accomplished in 10 of 22 primary tumors and in 7 of 10 SCC cell lines. Loss of heterozygosity of chromosome 17p, were the p53 gene is localized, was seen in five of seven SCC lines studied. DNA sequencing of the p53 gene of these five cell lines that had lost one allele showed p53 mutations in the remaining allele. In addition, from six primary SCC that exhibited loss of heterozygosity of chromosome 17p, three showed missense mutations of the p53 gene. The mutations of primary tumors and SCC cell lines were scattered in the midregion of the gene, affecting codons 151, 155, 174, 194, 220, 248, and 273. Five of these mutations modified guanine residues, a phenomenon that has been associated with the effect of carcinogens contained in tobacco smoke. Collectively these data show that approximately 50% of primary tumors and cell lines derived from SCC of the head and neck showed abnormalities of the p53 gene. In addition, it is of interest to note that the most invasive cell lines, as determined in an in vivo assay using xenotransplantation of tumor cells into denuded rat tracheal grafts, exhibited the most intense staining. Similarly, of five very advanced primary tumors, four showed intense p53 immunostain. These observations support the evidence that alterations in this tumor suppressor gene could be related to late events in tumor progression.
对一组22例头颈部原发性鳞状细胞癌（SCC）以及10株源自SCC的细胞系进行了p53改变的研究。22例原发性肿瘤中有10例以及10株SCC细胞系中有7例实现了p53的免疫组化阳性检测。在研究的7株SCC细胞系中，有5株出现了17号染色体短臂（17p）的杂合性缺失，而p53基因就定位在该染色体上。对这5株丢失了一个等位基因的细胞系的p53基因进行DNA测序，结果显示其余等位基因存在p53突变。此外，在6例出现17号染色体短臂杂合性缺失的原发性SCC中，有3例显示p53基因的错义突变。原发性肿瘤和SCC细胞系的突变分散在基因的中部区域，影响密码子151、155、174、194、220、248和273。这些突变中有5个修饰了鸟嘌呤残基，这一现象与烟草烟雾中所含致癌物的作用有关。总体而言，这些数据表明，约50%的头颈部SCC原发性肿瘤和细胞系显示p53基因异常。此外，值得注意的是，在将肿瘤细胞异种移植到去上皮大鼠气管移植物的体内试验中确定的侵袭性最强的细胞系，显示出最强的染色。同样，在5例非常晚期的原发性肿瘤中，有4例显示p53免疫染色强烈。这些观察结果支持了这样的证据，即这种肿瘤抑制基因的改变可能与肿瘤进展的晚期事件有关。
