Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma

Aims: The objectives of this study were: (1) to determine, using immunohist ochemistry, the level of expression of the cell cycle factors p53, p21 and cyclin D1 in a group of bronchioloalveolar carcinomas (BACs), and to compar e these data to relevant published data for lung carcinoma; (2) to determin e if higher expression rates for these factors in BAC were associated stati stically with advanced clinical stage, greater tumour size, tobacco abuse, and/or BAC subtype; (3) to seek, using Fisher's exact t-test and paired dat a groups, any significant associations within the expression data for p53, p21 and cyclin D1. Methods and results: A panel of monoclonal antibodies against p53, p21 and cyclin D1 was applied to 19 bronchioloalveolar carcinomas (17 surgical path ology cases and two autopsies) from the tissue archives of St. Louis Univer sity. These immunohistochemical stains were graded on a semiquantitative sc ale according to the prevalence of nuclear staining within the tumour (<10% positive cells = 0, 10-25% = 1+, 25-50%=2+, 50-75%=3+ and 75-100%=4+). Six of 19 (32%) of BACs showed 1+ or greater p53 positivity, six of 19 (32%) s howed If or greater nuclear cyclin D1 positivity, and nine of 19 (47%) of B ACs showed 1+ or greater p21 nuclear positivity. A statistically significan t correlation was found between p53 and cyclin D1 expression (P = 0.046, Fi sher's exact t-test), but not between p53 and p21, or between p21 and cycli n D1. No statistically significant association was found between the cell c ycle factor expression data and subtype of BAC (mucinous vs. nonmucinous), tumour diameter, clinical stage or tobacco-use history. Conclusions: BACs show p53 immunostain positivity at a frequency similar to that published for p53 mutations in lung adenocarcinomas in general. Cycli n D1 and p21 nuclear expression characterizes a significant proportion of B ACs, with cyclin D1 and p53 expression showing a statistically significant association, Aberrations in p53, p21, and cyclin D1 expression map be impor tant in the development of a significant proportion of BACs.