Zheng J, Shu Q, Li Z H, Tsao J I, Weiss L M, Shibata D
Department of Pathology, University of Southern California School of Medicine, Los Angeles.
Am J Pathol. 1994 Dec;145(6):1444-9.
Squamous cell carcinoma (SQCC) of the lung is thought to arise after the accumulation of multiple mutations, including p53. To better characterize when p53 mutations are acquired, 37 SQCC of the lung were examined by polymerase chain reaction and single-strand conformation polymorphism analysis. Somatic p53 mutations were detected in nine tumors (24.3%). There were no significant differences in the stage, sex, or race between patients with or without p53 mutations. However, the patients with SQCC and p53 mutations were significantly (P = 0.0006) younger (mean age, 54.3 years) compared with patients without p53 mutations (mean age, 65). The topographical tissue distributions of the p53 mutations were examined by selective ultraviolet radiation fractionation. In all nine cases, the specific p53 mutant alleles were homogeneously present throughout the primary tumors, in all three examples with in situ carcinoma, and in all four cases with metastases. In one case, squamous metaplasia contiguous with the primary tumor also contained the same p53 mutation. Normal or hyperplastic and metaplastic or dysplastic epithelium not contiguous with the primary tumors lacked the specific p53 mutations. These findings suggest that p53 mutations are commonly acquired at a relatively early age, before the bulk of clonal expansion, and usually persist throughout the progression of SQCC of the lung.
肺鳞状细胞癌（SQCC）被认为是在包括p53在内的多个突变积累后发生的。为了更好地描述p53突变何时获得，通过聚合酶链反应和单链构象多态性分析对37例肺SQCC进行了检查。在9个肿瘤（24.3%）中检测到体细胞p53突变。有或没有p53突变的患者在分期、性别或种族方面没有显著差异。然而，与没有p53突变的患者（平均年龄65岁）相比，患有SQCC和p53突变的患者明显更年轻（平均年龄54.3岁，P = 0.0006）。通过选择性紫外线辐射分级检查p53突变的地形组织分布。在所有9例中，特定的p53突变等位基因在整个原发性肿瘤、所有3例原位癌以及所有4例转移瘤中均均匀存在。在1例中，与原发性肿瘤相邻的鳞状化生也含有相同的p53突变。与原发性肿瘤不相邻的正常或增生性以及化生或发育异常的上皮缺乏特定的p53突变。这些发现表明，p53突变通常在相对较早的年龄获得，在大部分克隆扩增之前，并且通常在肺SQCC的进展过程中持续存在。
