To clarify the events leading to the disruption of cell growth control that occurs during the development of pulmonary adenocarcinoma (AC), we used immunohistochemistry to evaluate the expression of G1 cycle regulators, cyclin D1, Rb protein (pRb), and p16 MTS1 protein and the tumour proliferation marker, Ki 67, both in AC of the lung and in its precursor lesion, atypical adenomatous hyperplasia (AAH). The frequency of lesions with cyclin D1 overexpression was relatively high in AAH (47-89%), but was decreased in early AC (28%) and overt AC (35%). The loss of pRb expression was rare in both AAH (0-18%) and early AC (0%), and was infrequent even in overt AC (13%). The loss of p16 expression was also relatively infrequent in both the premalignant and the malignant lesions (11-25%). Our results suggest that overexpression of cyclin D1 is an early event and plays an important part in tumorigenesis in the case of lung AC. However, cyclin D1 overexpression is not required for the development and maintenance of a malignant phenotype. It is likely that some cyclin D1-independent pathways other than Rb and p16 abnormalities have an important role in the malignant transformation from AAH to early AC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.