Phenotypically Different Cells with Heterogeneous Nuclear Ribonucleoprotein A2/B1 Overexpression Show Similar Genetic Alterations

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.