Phenotypically different cells with heterogeneous nuclear ribonucleoprotein A2/B1 overexpression show similar genetic alterations

Immunocytochemical studies have revealed that overexpression of heterogeneo us nuclear ribonucleoprotein (hnRNP) A2/B1 in exfoliated epithelial cells i s a potentially useful marker of early lung cancer. This study analyzed the correlation of hnRNP A2/B1 expression with molecular alterations in phenot ypically different epithelial cells of paraffin-embedded pulmonary tissues. Sections from 20 human subjects were analyzed immunohistochemically for ex pression of hnRNP A2/B1, Normal-appearing, hyperplastic, and malignant epit helial cells with and without hnRNP A2/B1 expression (n = 78) were microdis sected and assessed for microsatellite alterations (MA) and loss of heteroz ygosity (LOH) (n = 14 markers) as well as for clonality. Results showed tha t (I) hnRNP A2/B1 immunoreactive cells contained a significantly higher fre quency 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 norma l-appearing and hyperplastic cells persisted in malignant cells; (3) prelim inary analysis of methylation status of the androgen receptor gene in non-n eoplastic cells was suggestive of hnRNP A2/B1-expressing cells being of clo nal 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 differen t respiratory epithelial cells with hnRNP A2/B1 overexpression might be clo nally derived, and that the subcellular localization of hnRNP A2/B1 might b e an important factor associated with tumor progression.