Expression of peptidyl-glycine alpha-amidating mono-oxygenase (PAM) enzymes in morphological abnormalities adjacent to pulmonary tumors.

Carboxyl-terminal amidated peptide hormones are known to be autocrine growth factors for lung tumors and tumor cell lines. Expression of the enzymes necessary for the biosynthesis of active amidated peptide hormones is therefore necessary for autocrine growth stimulation in lung tumors and possibly in the early proliferative stages of lung carcinogenesis. The peptidyl amidating enzymes have previously been identified in cell lines of all histological types of lung cancer and in lung tumors by immunohistochemistry and in situ hybridization. In this study we analyzed the expression of the peptidyl amidating enzymes in histological abnormalities found in the proximity of pulmonary tumors from a series of 59 patients. Most of the lesions in both the proximal airways (basal cell hyperplasia, carcinoma in situ, and some squamous metaplasia) and the alveoli (type II cell hyperplasia, bronchiolization of the alveoli, atypical alveolar hyperplasia, and isolated atypias) had a high proportion of cells strongly positive for the peptidyl amidating enzymes. The intense expression of peptidyl amidating enzymes in type II cell hyperplasia and atypical alveolar cells, together with the high frequency of these abnormalities in the alveoli, which is an area that does not express these enzymes in normal lung, points to the involvement of peptide hormones in the growth biology of pulmonary tumors. These findings suggest that peptide hormone stimulation of mitogenesis is an early event in tumor progression and merits additional investigation as a target for early detection and chemo-intervention of lung carcinogenesis.