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Frédéric Mouriaux, Claude-Alain Maurage, Pierre Labalette, Bernard Sablonnière, François Malecaze, Jean-Marie Darbon; Cyclin-Dependent Kinase Inhibitory Protein Expression in Human Choroidal Melanoma Tumors. Invest. Ophthalmol. Vis. Sci. 2000;41(10):2837-2843.
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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
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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