Expression of surfactant protein mRNA in normal and neoplastic lung of B6C3F(1) mice as demonstrated by in situ hybridization

The localization of surfactant protein (SP), A, B, C, and D mRNAs was exami ned in B6C3F(1) mice in the normal lung, and in a range of spontaneous prol iferative lung lesions using nonisotopic in situ hybridization (ISH). The a im was to develop diagnostic markers, and if possible, throw further light on the histogenesis of these lesions. Tissues from 21 animals were examined , the lesions studied were: 4 alveolar epithelial hyperplasias, 12 alveolar /bronchiolar (A/B) adenomas, and 5A/B carcinomas. Lung metastases of hepato cellular carcinoma (HCC) were used as controls. In the nonneoplastic lung, staining for SP A, B, and C mRNA was observed in normal and hyperplastic ty pe II cells but not in the bronchiolar epithelium. SP mRNAs were present in all lung tumors, with SPs A, B, and C being coexpressed in 10/12 (83%) of adenomas and 4/5 (80%) of carcinomas in both solid and tubulopapillary area s. No signals for SP D mRNA were noted in normal or neoplastic lung. Additi onally, no staining for any SP transcript was observed in the HCC metastase s examined. In summary, ISH for SP A, B, or C mRNA was a helpful aid in the diagnosis of proliferative lesions of the murine lung, enabling differenti ation from hepatocellular metastases. Furthermore, this work provides stron g support for the proposal that spontaneous lung tumors in B6C3F(1) mice ar e of alveolar, not bronchiolar origin, and consistently show type II cell d ifferentiation. We suggest that such tumors should be referred to as alveol ar adenomas and carcinomas.