Man Y G, Martinez A, Avis I M, Hong S H, Cuttitta F, Venzon D J, Mulshine J L
Department of Cell and Cancer Biology, and Biostatistics and Data Management Section, Medicine Branch, Division of Clinical Science, National Cancer Institute, Bethesda, Maryland 20892, USA.
Am J Respir Cell Mol Biol. 2000 Nov;23(5):636-45. doi: 10.1165/ajrcmb.23.5.4177.
Immunocytochemical studies have revealed that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/ B1 in exfoliated epithelial cells is a potentially useful marker of early lung cancer. This study analyzed the correlation of hnRNP A2/B1 expression with molecular alterations in phenotypically different epithelial cells of paraffin-embedded pulmonary tissues. Sections from 20 human subjects were analyzed immunohistochemically for expression of hnRNP A2/B1. Normal-appearing, hyperplastic, and malignant epithelial cells with and without hnRNP A2/B1 expression (n = 78) were microdissected and assessed for microsatellite alterations (MA) and loss of heterozygosity (LOH) (n = 14 markers) as well as for clonality. Results showed that (1) hnRNP A2/B1 immunoreactive cells contained a significantly higher frequency of MA and LOH than did comparable cells that lacked detectable hnRNP A2/B1; (2) over 80% of MA and LOH seen in hnRNP A2/B1 immunoreactive normal-appearing and hyperplastic cells persisted in malignant cells; (3) preliminary analysis of methylation status of the androgen receptor gene in non-neoplastic cells was suggestive of hnRNP A2/B1-expressing cells being of clonal origin; and (4) cells with cytoplasmic hnRNP A2/B1 immunoreactivity had a 3-fold higher frequency of MA and LOH than did cells with nuclear hnRNP A2/B1 immunoreactivity. These findings suggest that phenotypically different respiratory epithelial cells with hnRNP A2/B1 overexpression might be clonally derived, and that the subcellular localization of hnRNP A2/B1 might be an important factor associated with tumor progression.
免疫细胞化学研究表明，脱落上皮细胞中异质性核核糖核蛋白（hnRNP）A2/B1的过表达是早期肺癌的一个潜在有用标志物。本研究分析了石蜡包埋肺组织中hnRNP A2/B1表达与表型不同的上皮细胞分子改变之间的相关性。对20名人类受试者的切片进行hnRNP A2/B1表达的免疫组织化学分析。对有和没有hnRNP A2/B1表达的正常外观、增生性和恶性上皮细胞（n = 78）进行显微切割，并评估微卫星改变（MA）和杂合性缺失（LOH）（n = 14个标志物）以及克隆性。结果显示：（1）hnRNP A/B1免疫反应性细胞中MA和LOH的频率显著高于缺乏可检测到的hnRNP A2/B1的对照细胞；（2）在hnRNP A2/B1免疫反应性正常外观和增生性细胞中观察到的超过80%的MA和LOH在恶性细胞中持续存在；（3）对非肿瘤细胞中雄激素受体基因甲基化状态的初步分析提示，表达hnRNP A2/B1的细胞起源于克隆；（4）细胞质中具有hnRNP A2/B1免疫反应性的细胞中MA和LOH的频率比细胞核中具有hnRNP A2/B1免疫反应性的细胞高3倍。这些发现表明，hnRNP A2/B1过表达的表型不同的呼吸道上皮细胞可能起源于克隆，并且hnRNP A2/B1的亚细胞定位可能是与肿瘤进展相关的一个重要因素。
