Herfarth K K, Wick M R, Marshall H N, Gartner E, Lum S, Moley J F
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Genes Chromosomes Cancer. 1997 Sep;20(1):24-9.
The role of the TP53 gene in the development of inherited and sporadic pheochromocytomas and medullary thyroid carcinomas (MTC) has not been clarified because of conflicting reports and limitations in the assays used to detect mutations. To determine the frequency of TP53 alterations in these tumors, 22 pheochromocytomas and 29 MTCs were screened for loss of heterozygosity (LOH) on 17p with four markers. Single-strand-conformation-variant (SSCV) analysis of exons 4-9 of the TP53 gene was performed in 20 of the pheochromocytomas and in 22 of the MTCs. The expression of p53 was determined by immunohistochemistry in 19 pheochromocytomas and in 17 MTCs using two antibodies (D01 and D07) on frozen and paraffin-embedded tissues. Four of the 22 pheochromocytomas and none of the MTCs showed LOH on 17p. No mutations were detected in any of the tumors screened by SSCV analysis. Immunohistochemical staining of frozen and paraffin-embedded tumor sections did not show p53 overexpression in any of the tumors examined. Our findings indicate that mutations in the TP53 gene are an uncommon event in the tumorigenesis of pheochromocytomas and medullary thyroid carcinomas.
由于相互矛盾的报道以及用于检测突变的分析方法存在局限性，TP53基因在遗传性和散发性嗜铬细胞瘤以及甲状腺髓样癌（MTC）发生发展中的作用尚未明确。为了确定这些肿瘤中TP53改变的频率，对22例嗜铬细胞瘤和29例MTC进行了检测，使用四个标记物筛查17p上的杂合性缺失（LOH）。对20例嗜铬细胞瘤和22例MTC进行了TP53基因第4至9外显子的单链构象变异（SSCV）分析。在19例嗜铬细胞瘤和17例MTC中，通过免疫组织化学方法，使用两种抗体（D01和D07）在冰冻和石蜡包埋组织上检测p53的表达。22例嗜铬细胞瘤中有4例在17p上显示杂合性缺失，而MTC中无一例显示。通过SSCV分析筛查的任何肿瘤中均未检测到突变。冰冻和石蜡包埋肿瘤切片的免疫组织化学染色在任何检测的肿瘤中均未显示p53过表达。我们的研究结果表明，TP53基因突变在嗜铬细胞瘤和甲状腺髓样癌的肿瘤发生中是不常见的事件。
