Independent prognostic role of p16 expression in lung cancer

Objectives: The cyclin-dependent kinase p16 (also known as Ink4A, Mts1, Cdk n2, and Cdkn4i) has been proposed as a tumor suppressor gene mapped on chro mosome segment 9p21, This study evaluated p16 protein expression in 135 lun g cancer specimens and investigated potential genetic alterations occurring in this gene. Results: We found altered p16 immunohistochemical expression to be a frequent event in lung cancer and to be independent of either the histologic type or any other clinical-pathologic feature, Western blot anal yses performed on about one third of the specimens correlated highly with t hese results, In addition, we found p16 immunohistochemical expression to b e a favorable prognostic factor in lung cancer in that its reduction or los s correlated with a worse outcome for the patients. Polymerase chain reacti on amplification and direct sequencing of p16 exons 1 and 2 revealed no mut ations, indicating that p16-altered expression in lung cancer is not necess arily linked to mutational events of these genes. Conclusions: We conclude that p16-altered expression is both an independent and frequent event in lu ng cancer and may have an important role in tumorigenesis and in malignant progression of a significant proportion of these cancers. However, the actu al incidence and relevance of p16 mutations in this neoplasm continues to b e debated, and its analysis seems inconclusive, Our results suggest a progn ostic role for the immunodetection of this protein on formalin-fixed and pa raffin-embedded specimens. They further suggest its routine use in the eval uation of the frequently unpredictable behavior of lung cancer.