title: Phenotypically different cells with heterogeneous nuclear ribonucleoprotein A2/B1 overexpression show similar genetic alterations.
abstract: 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.
authors.affiliation: 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.
authors.forename: Y G
authors.initials: YG
authors.lastname: Man
authors.forename: A
authors.initials: A
authors.lastname: Martinez
authors.forename: I M
authors.initials: IM
authors.lastname: Avis
authors.forename: S H
authors.initials: SH
authors.lastname: Hong
authors.forename: F
authors.initials: F
authors.lastname: Cuttitta
authors.forename: D J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: J L
authors.initials: JL
authors.lastname: Mulshine
mesh_terms: D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017411:Ribonucleoproteins, Small Nuclear / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D017411:Ribonucleoproteins, Small Nuclear