Iggo R, Gatter K, Bartek J, Lane D, Harris A L
ICRF Molecular Immunochemistry Laboratory, Potter's Bar, Hertfordshire.
Lancet. 1990 Mar 24;335(8691):675-9. doi: 10.1016/0140-6736(90)90801-b.
Primary lung cancer samples of the major histological types were examined for expression of the tumor suppressor gene p53 by immunohistochemistry. Abnormalities in p53 expression were found in 28 of 40 carcinomas, 14 of 17 squamous tumours showing abnormal p53 expression, whereas no expression of p53 was detectable in 7 carcinoid tumours or in 10 normal lung samples. Direct evidence for homozygous expression of mutant p53 mRNA in representative carcinomas was obtained by means of an asymmetric polymerase chain reaction mRNA sequencing strategy, which allowed sequencing without any cloning step. All the mutations were G to T transversions resulting in mis-sense mutations in aminoacids highly conserved in evolution. Mutation of the p53 gene is the most frequently identified genetic change in human lung cancer; these findings suggest that simple immunohistological methods can provide strong evidence of such mutation.
通过免疫组织化学方法检测主要组织学类型的原发性肺癌样本中肿瘤抑制基因p53的表达情况。在40例癌组织中有28例发现p53表达异常，17例鳞状肿瘤中有14例显示p53表达异常，而在7例类癌肿瘤或10例正常肺样本中未检测到p53表达。采用不对称聚合酶链反应mRNA测序策略，在代表性癌组织中获得了突变型p53 mRNA纯合表达的直接证据，该策略无需任何克隆步骤即可进行测序。所有突变均为G到T的颠换，导致在进化过程中高度保守的氨基酸发生错义突变。p53基因的突变是人类肺癌中最常发现的基因变化；这些发现表明，简单的免疫组织学方法可以为此类突变提供有力证据。
