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皮肤恶性黑色素瘤中不同的细胞增殖、死亡模式及癌基因表达

Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma.

作者信息

Miracco C, Santopietro R, Biagioli M, Lazzi S, Nyongo A, Vatti R, Luzi P

机构信息

Institute of Pathological Anatomy and Histology, University of Siena, Italy.

出版信息

J Cutan Pathol. 1998 May;25(5):244-51. doi: 10.1111/j.1600-0560.1998.tb01728.x.

DOI:10.1111/j.1600-0560.1998.tb01728.x
PMID:9696289
Abstract

Ninety-six cutaneous melanomas (CMs) were investigated aiming at finding differences, if any, among the main four clinicopathological types, for Bcl-2, c-myc and p53 protein expression, and for tumor cell proliferation and death indices. Proliferation was assessed by calculating the mitotic index (MI, number of mitoses) and the MIB1 labelling index (M-LI, number of MIB1+ nuclei), and tumor cell death by calculating the 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 especially in thicker superficial spreading (SSM) and lentigo maligna melanoma (LMM) types. p53 Expression was higher in nodular melanoma (NM) and in acral lentiginous 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 apoptotic death, whereas c-myc and p-53 genes promote this process. In CMs, no relation was found between Bcl-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.

摘要

对96例皮肤黑色素瘤(CM)进行了研究,旨在找出四种主要临床病理类型之间在Bcl-2、c-myc和p53蛋白表达以及肿瘤细胞增殖和死亡指数方面是否存在差异。通过计算有丝分裂指数(MI,有丝分裂数)和MIB1标记指数(M-LI,MIB1阳性细胞核数)评估增殖情况,通过计算1000个肿瘤细胞中的凋亡指数(AI,凋亡数)评估肿瘤细胞死亡情况。CM被细分为薄型(<1mm)和中等厚度(1-4mm)肿瘤。不同类型之间Bcl-2表达无显著变化。c-myc表达尤其在较厚的浅表扩散型(SSM)和恶性雀斑样痣黑色素瘤(LMM)类型中降低。p53表达在结节性黑色素瘤(NM)和肢端雀斑样痣黑色素瘤(ALM)中较高,这两种类型也显示出最高程度的增殖。薄型SSM、LMM和ALM的AI显著高于中等厚度的同类肿瘤(分别为8.4对2;6.1对2.3,以及5.8对3.6)。薄型(1.7)和中等厚度(1.9)的NM的AI较低,它们的MI(分别为3.9和4.5)和M-LI(分别为16.7和2.9)较高。薄型和中等厚度的ALM也显示出较高的MI和M-LI(分别为4.1对5.2和11.3对14.6)。Bcl-2是抑制凋亡死亡的基因之一,而c-myc和p-53基因促进这一过程。在CM中,未发现Bcl-2表达、MI、PI和AI之间存在关联。所有AI高的SSM、LMM和ALM均显示c-myc高表达且p53阴性。c-myc虽然高表达,但在NM类型中并未促进显著的凋亡死亡。在所有CM中,Bc12、c-myc和p53的表达不均衡,与肿瘤细胞更新的关系也不相同,这表明它们对不同类型和阶段有不同影响,以及其他因素在CM生长控制中的作用。

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