P21 RNA AND PROTEIN EXPRESSION IN NON-SMALL-CELL LUNG CARCINOMAS - EVIDENCE OF P53-INDEPENDENT EXPRESSION AND ASSOCIATION WITH TUMORAL DIFFERENTIATION

p21, the product of the WAF1/CIP1/SDI1/mda-6 gene, is an inhibitor of cyclin-dependent kinases. In cell cultures p21 is induced by p53-depen dent and p53-independent pathways by DNA damage and induction of diffe rentiation. We investigated p21 RNA and immunohistochemical expression in 43 non-small cell lung carcinomas and corresponding normal lung sa mples previously investigated for p53 and WAF1 gene status and p53 pro tein expression. p21 RNA and protein expression in normal and neoplast ic tissues were strictly associated (P=0.0001). In normal tissue p21 R NA was expressed at low levels and p21 immunoreactivity was seen in sc attered differentiated bronchial, alveolar and stromal cells. In the m ajority of neoplasms p21 protein and RNA were expressed at higher leve ls than in the corresponding normal tissues: p21 overexpression was se en in 27 (63%) and 28 (65%) cases respectively. p21 was expressed inde pendently from p53 gene/protein alterations. p21 overexpression was mo re frequent in well differentiated tumors (P=0.01 and P=0.022 for RNA and protein respectively), and p21 immunoreactivity was usually seen i n foci of more pronounced differentiation. We conclude that p21 expres sion is related to tumor differentiation, and that p53-independent p21 expression is a common feature of in vivo neoplasms.