Gouyer V, Gazzeri S, Brambilla E, Bolon I, Moro D, Perron P, Benabid A L, Brambilla C
Laboratoire de Pathologie Cellulaire, Université Joseph Fourier, Centre Hospitalier Albert Michallon, Grenoble, France.
Int J Cancer. 1994 Sep 15;58(6):818-24. doi: 10.1002/ijc.2910580612.
RB protein expression and loss of heterozygosity (LOH) in the RB gene were studied in 77 primary lung carcinomas of all histological types. RB protein expression was studied by immunohistochemistry with 3 anti-RB antibodies, and was found altered in 23/29 (79%) neuro-endocrine (NE) carcinomas and in 18/48 (37%) non-NE carcinomas. RB gene allele status was studied with 3 probes detecting RFLP in RB locus. Fifty-five patients were informative, and loss of heterozygosity was detected in 29 (52%) of the corresponding tumors with 1 of the 3 probes used; 89% of the informative NE carcinomas, excluding carcinoids, and only 13% of the non-NE carcinomas exhibited LOH and loss of RB-protein expression. LOH at the RB locus was strongly correlated with the absence of RB protein in malignant NE carcinomas, and this association was strongly correlated with the neuro-endocrine phenotype. Inactivation of the RB protein in primary NE carcinomas, excluding carcinoids, therefore seems to imply in the majority of cases the mutation of one allele and loss of the remaining allele of the RB gene, leading to loss of RB-protein expression. In contrast, RB-protein expression was independent of allele status in non-NE carcinomas and carcinoids.
在77例所有组织学类型的原发性肺癌中研究了RB蛋白表达及RB基因杂合性缺失（LOH）情况。采用3种抗RB抗体通过免疫组织化学法研究RB蛋白表达，结果发现23/29（79%）例神经内分泌（NE）癌及18/48（37%）例非NE癌中RB蛋白表达发生改变。采用3种在RB基因座检测限制性片段长度多态性（RFLP）的探针研究RB基因等位基因状态。55例患者信息明确，在相应肿瘤中，使用的3种探针之一检测到29例（52%）存在杂合性缺失；除类癌外，89%的信息明确的NE癌及仅13%的非NE癌表现出杂合性缺失及RB蛋白表达缺失。RB基因座的杂合性缺失与恶性NE癌中RB蛋白缺失密切相关，且这种关联与神经内分泌表型密切相关。因此，除类癌外，原发性NE癌中RB蛋白失活在大多数情况下似乎意味着RB基因一个等位基因突变及另一个等位基因缺失，导致RB蛋白表达缺失。相比之下，在非NE癌和类癌中，RB蛋白表达与等位基因状态无关。
