Cyclin-dependent kinase inhibitory protein express in human choroidal melanoma tumors

PURPOSE. Recent studies have demonstrated the close link between oncogenesi s and cell cycle machinery. Cyclin-dependent kinase inhibitory proteins (CK Is) have been shown to play a critical role in the regulation of cell cycle progression. Alteration of CKI levels and/or functions could be implicated in cell transformation. The three CKIs-p16, p21, and p27-were investigated in human uveal melanoma tumors, and an attempt was made to correlate their levels with clinicopathologic parameters, as well as to p53 and Ki-67 (Mib -1) protein levels. METHODS. Immunochemistry was performed on 32 formalin-fixed, paraffin-embed ded specimens of malignant choroidal melanoma. Immunoblot was performed to confirm the immunochemistry study. Prognostic histologic markers such as ce ll typing, pigmentation, larger tumor dimension, mitotic figures, nucleolar size, scleral invasion, and optic nerve head invasion were reported. RESULTS. Nuclear positivity for p16 was observed in 11 tumors (34%) without any association with clinicopathologic parameters. Tumor cells positive fo r p21 were detected in 12 choroidal melanomas (37%). Unexpectedly, a positi ve relationship was seen between p21 and scleral invasion (P = 0.008). Nucl ear positivity for p27 was observed in nine tumors (28%). An inverse correl ation was observed between the number of mitotic figures and p27 immunoreac tivity (P = 0.03), as well as between Mib-1 positivity and p27 expression ( P = 0.02). Western blot assays of tumor extracts confirmed overexpression o f p21 and p27. CONCLUSIONS. The results suggest that p21 and p27 may be involved in tumori genesis in choroidal melanoma.