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Cyclin-Dependent Kinase Inhibitory Protein Expression in Human Choroidal Melanoma Tumors

¹ From the Division of Ophthalmology, Huriez Hospital; the ² Division of Pathology, Calmette Hospital; and the ³ Division of Biochemistry, Salengro Hospital, Lille, France; and the ⁴ Institut National de la Santé et Recherche Médicale CJF 95-10, Pavillon Rayer, Purpan Hospital, Toulouse, France.

PURPOSE. Recent studies have demonstrated the close link between oncogenesis and cell cycle machinery. Cyclin-dependent kinase inhibitory proteins (CKIs) 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-embedded specimens of malignant choroidal melanoma. Immunoblot was performed to confirm the immunochemistry study. Prognostic histologic markers such as cell 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 for p21 were detected in 12 choroidal melanomas (37%). Unexpectedly, a positive relationship was seen between p21 and scleral invasion (P = 0.008). Nuclear positivity for p27 was observed in nine tumors (28%). An inverse correlation was observed between the number of mitotic figures and p27 immunoreactivity (P = 0.03), as well as between Mib-1 positivity and p27 expression (P = 0.02). Western blot assays of tumor extracts confirmed overexpression of p21 and p27.

CONCLUSIONS. The results suggest that p21 and p27 may be involved in tumorigenesis in choroidal melanoma.

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