Downregulation of cell cycle modulators p21, p27, p53, Rb and proapoptotic Bcl‐2‐related proteins Bax and Bak in cutaneous melanoma is associated with worse patient prognosis: preliminary findings

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Abstract
Cutaneous melanoma is a tumor with high metastatic potential, but the mechanisms leading to progression are still not fully understood. To provide further molecular basis for understanding the progression of melanoma, the aim of this study was to examine the expression pattern of cell cycle modulators (p21, p27, p53 and Rb) and proapoptotic multidomain Bcl-2 related proteins (Bax and Bak) and to analyze its differences in patients with and without progression stages. We have studied 31 patients with cutaneous melanoma at stage IIa (Breslow thickness 1.5-4.0 mm), and follow them for 10-year period. Eighteen of these patients developed metastasis. The determination of selected molecular markers participating in cell cycle regulation and apoptosis was performed by immunohistochemistry. We have observed a significant increase in the loss of expression of the Bax, Bak, p21, p27, p53 and Rb. The analysis of the relationship between these downregulated markers and Breslow thickness showed significant positive correlation (r=0.556, p=0.029) and predictive value if thickness below 2.3 mm (OR=3.0, 95% CI=0.312-28.84). Our study showed that the downregulation of the markers associated with cell cycle control and apoptosis is of great value in predicting malignant transformation and in assessing the risk of metastases development for 10-year follow-up period.