Correlation of cell cycle regulatory proteins (p53 and p16ink4a) and bcl-2 oncoprotein with mitotic index and thickness of primary cutaneous malignant melanoma

Miloš Kostov,Snežana Cerović,Žaklina Mijović,Marija Jelić,Miroslav Stojanović,Dragan Mihailović

doi:10.17305/bjbms.2010.2660

Miloš Kostov, Snežana Cerović + Show 4 more

Open Access

https://doi.org/10.17305/bjbms.2010.2660

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Abstract

The purpose of the study was to determine the frequency of expression p53 and p16INK4a proteins and bcl-2 oncoprotein in malignant skin melanoma and to determine their correlation with the proliferative index and tumor thickness. The study involved 53 patients: 27 (51%) male and 26 (49%) female. Mitotic index showed a correlation with p53 protein expression, a negative correlation with p16INK4a protein expression. Statistically significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p53 protein expression, as well as Breslow tumor thickness and bcl-2 oncoprotein expression (p<0.05), whereas there was no correlation between the p16INK4a protein expression and melanoma thicknes and Clark invasion level. Overexpression p53 protein and bcl-2 oncoprotein, with the loss p16INK4a protein of expression in the nodular melanoma, confirms a frequent loss of function of these tumor suppressor gene and oncogene, and indicates a vertical tumor growth phase. The loss of tumor suppression function the p53 protein and bcl-2 oncoprotein overexpression in cutaneous melanoma correlates with larger tumor thickness, whereas the overexpression of mutated p53 protein and loss p16INK4a protein of expression indicate a higher proliferative tumour potential. Therefore, these evaluated proteins may be the aggressive biological tumour activity markers.

Highlights

Malignant melanoma of the skin (MMS) is a melanocyte system tumor which is produced by the malignant melanocyte transformation generated by the neural crest [, ]
Significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p protein expression, as well as Breslow tumor thickness and bcl- oncoprotein expression (p< . ), whereas there was no correlation between the p INK a protein expression and melanoma thicknes and Clark invasion level
Our results show that there is no correlation between the Breslow tumor thickness and Clark invasion level degree compared to p protein expression, which is confirmed by other authors [, ]

Summary

Introduction

Malignant melanoma of the skin (MMS) is a melanocyte system tumor which is produced by the malignant melanocyte transformation generated by the neural crest [ , , ]. MMS is characterized by high malignant potential and high mortality rate, as well as a rapid occurrence rate in the late years, especially in women [ ]. Multistep tumorigenesis is an evolving process that involves the inactivation of tumor suppressor genes, activation of oncogenes and defects of the reparatory genes which can induce inadequate gene reparation [ ]. The most common oncogene defect occurs at the control site G /S which mediates the cell S phase onset [ - ]. Melanoma is not an exception in the tumor biology and its occurrence is predominantly the result of the gene mutations accumulation whose key role is the regulation of cellular proliferation, differentiation, apoptosis or some other pathways of cellular death [ , ].

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