Correlation of nuclear morphometry of primary melanoma of the skin with clinicopathological parameters and expression of tumor suppressor proteins (p53 and p16(INK4a)) and bcl-2 oncoprotein.

Purpose: To determine the correlation of nuclear morphometry of primary cutaneous malignant melanoma (CMM) with clinicopathological parameters and the expression of p53, p16INK4a, and bcl-2. Methods: Image analysis and computerized nuclear morphometry were used in a series of 53 primary CMM (nodular melanoma/NM, N=33, and superficially spreading melanoma/SSM, N=20). The clinicopathological parameters determined for each tumor were histological type, maximal tumor diameter, Breslow thickness, Clark level, ulceration, mitotic index (MI) and pathological disease stage. Measured nuclear features included size, shape and optical density (OD). The results were correlated with the expression of p53, p16INK4a and bcl-2. Results: Significant differences between NM and SSM were found for the nuclear area, OD, and perimeter (p<0.05). MI showed significant correlations with nuclear area, perimeter and Feret diameter (p<0.05). In relation to the Clark level, significant differences were found for OD (p<0.01) and circularity of nuclei (p<0.05) between levels II and IV, while the Breslow thickness was not significantly correlated with nuclear morphometric variables. Significantly negative correlations were observed between OD and the expression of p53 and bcl-2, while significant positive correlation was found between the nuclear circularity and p53 immunoreaction intensity. There was no significant correlation between the expression of p16INK4a protein and karyometric variables. Conclusion: OD and circularity are SIGNIFICANTLY correlated with p53 and bcl-2, and nuclear area with MI. These karyometric variables may determine a more aggressive phenotype of melanoma cells.