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Heterogeneous Nuclear Ribonucleoprotein A2/B1 Up-Regulation in Bronchial Lavage Specimens: A Clinical Marker of Early Lung Cancer Detection¹

Molecular Genetics Unit, Roy Castle International Centre for Lung Cancer Research, Liverpool L3 9TA [P. F., W. P., J. K. F.]; Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences [P. F., W. P., J. K. F.] and Department of Pathology [L. T.], University of Liverpool, Liverpool L69 3BX; and Cardiothoracic Centre [M. W.], Liverpool L14 3PE, United Kingdom

This study examines the use of a new epithelial marker in the detection of early lung cancer in bronchial lavage samples. The monoclonal antibody 703D4 recognizes the heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, and its overexpression/up-regulation was assessed and compared with routine diagnostic cytology. One hundred and three individuals were recruited into a prospective study. These individuals were referred to a chest physician with a request to examine for possible lung cancer, and a full clinical work-up was undertaken, including bronchoscopy and radiological investigations. In this study, we analyzed hnRNP expression in individuals with metaplastic bronchial epithelial cells or tumor cells in the bronchial lavage specimens, in a blinded study. The results from 103 bronchial lavage specimens indicate that hnRNP overexpression was more accurate in detecting evidence of a neoplasia than routine cytological examination. Twenty-two of 23 specimens in which malignant cells were identified cytologically demonstrated overexpression of hnRNP A2/B1. However, in the 80 specimens that were reported as cytologically negative, 41 of 80 demonstrated hnRNP overexpression, and 29 of these individuals were shown to have a lung neoplasm based on radiological findings and/or the biopsy taken at the bronchoscopy. An additional 4 of these 41 patients were shown to have a lung neoplasm within 8 months of the initial bronchoscopy. In conclusion, detection of hnRNPA2/B1 in bronchial lavage specimens that contain metaplastic bronchial epithelial cells or cancer cells predicts the presence of a neoplasm with a sensitivity of 96%, 82%, specificity.

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