EXPRESSION OF HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2 B1 IN BRONCHIAL EPITHELIUM OF CHRONIC SMOKERS/

The monoclonal antibody 703D4, which binds heterogeneous nuclear ribon ucleoprotein A2/B1 (hnRNP A2/B1), has been reported to detect lung can cer more than a year earlier than routine chest X-ray or cytomorpholog y, To explore the biological basis of this detection, we studied the e xpression of this antigen in the central airways of smokers with evide nce of bronchial metaplasia using specimens from a previously reported , randomized retinoid chemoprevention trial. By analyzing 1078 availab le biopsy specimens from 147 individuals at baseline and 68 individual s who completed the intervention, we frequently detected overexpressio n of hnRNP A2/B1 in normal and abnormal bronchial epithelium (i.e., in 41% of normal and 37% of squamous metaplasia samples), There was Ho c orrelation between hnRNP A2/B1 overexpression and the different histol ogical changes. In cases with hnRNP A2/B1 overexpression, immunoreacti vity was homogeneously expressed in all biopsied sites, For the 68 cas es with serial biopsies, there was no significant modulation of hnRNP expression by retinoid intervention or smoking status. With lung cance r cell lines, 0.5-4 mu M concentrations of 13-cis-retinoic acid reduce d hnRNP A2/B1 overexpression by immunocytochemistry. We conclude that hnRNP A2/B1 overexpression is frequently found in central airways of c hronic smokers, consistent with the pattern of expression that we repo rted previously in airways surrounding resected primary lung cancers. Oral 13-cis-retinoic acid at a dose of 1 mg/kg has no demonstrable eff ects on modulating hnRNP A2/B1 expression in proximal bronchial epithe lium.