Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma
ABSTRACT Ninety-six cutaneous melanomas (CMs) were investigated aiming at finding differences, if any, among tbe main four chnicopatho-logical types, for Bcl-2. c-myc and p53 protein expression, and for tumor cell proliferation and death indices. Proliferation was assessed by calculating die mitotic index (MI, number of mitoses) and the MIBl labelling index (M-LI, number of MIBI+ nuclei), and tumor cell death by calculating tbe apoptotic index (AI, number of apoptoses) among 1000 tumor cells. CMs were subdivided into thin (<1 mm) and intermediate thickness (1-4 mm) tumors. Bcl-2 expression did not significantly change among different types, c-myc Expression decreased expecially in thicker superficial spreading (SSM) and lentigo maligna melanoma (LMM) types. p53 Expression was higher in nodular melanoma (NM) and in acral lentigiuous melanoma(ALM), which also showed the highest degrees of proliferation. AI was significantly higher in thin rather than in intermediate thickness SSMs, LMMs and ALMs (8.4 vs. 2; 6.1 vs. 2.3. and 5.8 vs. 3.6, respectively). AI was low in thin (1.7) and intermediate thickness (1.9) NMs. Which also showed high MI (3.9 and 4.5, respectively), and M-LI (16.7 and 2.9, respectively). Thin and intermediate thickness ALMs also showed high MI and M-LI (4.1 vs. 5.2 and 11.3 vs. 14.6, respectively). Bcl-2 is among genes which inhibit apopiotic death, whereas c-myc and p-53 genes promote this process. In CMs. no relation was found between BcI-2 expression, MI, PI, and AI. All SSMs, LMMs, and ALMs with a high AI showed a high c-myc expression and were negative for p53. c-myc, Although highly expressed, did not promote a significant apoptotic death in NM type. Bc12, c-myc, and p53 were not equally expressed nor equally related to tumor cell turnover in all CMs, suggesting their different influence on the various types and stages, and the role of other factors in CM growth control.