Variant expression of CD44 in preneoplastic lesions of the lung

BACKGROUND. Specific CD44 isoforms are cell surface adhesion molecules and have been shown to be associated with tumor progression and metastasis. In lung carcinoma, CD44 expression has been reported to be a feature of nonsma ll cell lung carcinoma (NSCLC) but not small cell lung carcinoma. A specifi c variant, CD44v6, was shown to be expressed only in a subset of NSCLC, nam ely the squamous cell and bronchoalveolar carcinomas, suggesting that CD44 may play a role in lung carcinoma differentiation. METHODS. To determine whether differential CD44 expression is an early even t in the pathogenesis of lung carcinoma, the authors investigated the patte rn of expression of the standard (CD44s) and variant (CD44v6) isoforms by i mmunohistochemistry in normal lung, nonneoplastic specimens, and bronchial biopsies of preneoplastic lesions. RESULTS. In normal bronchial epithelium and all nonneoplastic cases, CD44s expression was limited to the basement membrane and adjacent lower strata o f the epithelium, whereas CD44v6 was expressed within the basement membrane only. However, aberrant expression of both CD44s and CD44v6 was observed i n all preneoplastic lesions examined. In cases of dysplasia, squamous metap lasia, goblet cell hyperplasia, and basal cell hyperplasia, all epithelial strata showed immunoreactivity for both isoforms, in contrast to normal epi thelium, in which immunoreactivity was noted to be restricted to the basal layer cells. In contrast, CD44s and CD44v6 expression was completely absent in nearly all cases of adenomatosis. CONCLUSIONS. Altered CD44s and/or CD44v6 expression appears to be a feature of all preneoplastic lesions in the lung, the precise nature of which vari es according to histologic tumor type. Therefore, the authors conclude that CD44s and CD44v6 may lend themselves to be markers of preneoplastic change s in the lung. (C) 2001 American Cancer Society.