Mooy C M, Luyten G P, de Jong P T, Luider T M, Stijnen T, van de Ham F, van Vroonhoven C C, Bosman F T
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Am J Pathol. 1995 Oct;147(4):1097-104.
Neoplasia can be defined as deregulated tissue homeostasis caused by an imbalance between proliferation and apoptosis. Many genes are involved in the maintenance of tissue homeostasis, eg, the c-myc oncoprotein, which is an important regulator of cell proliferation and Bcl-2 protein, which is involved in the regulation of apoptosis. We studied retrospectively indices of proliferation, such as mitotic count and the Mib-1 index, on 51 uveal melanomas and compared their prognostic significance with established indicators of prognosis such as cell type and tumor size. Along the same line we investigated the expression of the regulating proteins c-myc and Bcl-2. Of all parameters tested, the largest tumor diameter and mitotic count were most strongly associated with tumor-related death (P < 0.001 and P = 0.005, respectively). In addition, cell type, the presence of epithelioid cells, the Mib-1 index, and the percentage of cytoplasmic c-myc-positive cells were significant predictive factors. Multivariate analysis showed that the Mib-1 index, largest tumor diameter, and the percentage of cytoplasmic c-myc-positive cells were independent prognostic parameters. Bcl-2 expression did not correlate with clinical outcome. The Mib-1 index correlated with the presence of epithelioid cells (P < 0.03) and the presence of apoptotic bodies (P < 0.001) and c-myc. A strong inverse relationship was found between (nuclear and cytoplasmic) c-myc and Bcl-2 (P < 0.00004 and P < 0.006, respectively), suggesting that Bcl-2 cooperates with c-myc to immortalize uveal melanoma cells.
肿瘤形成可定义为由增殖与凋亡失衡导致的组织稳态失调。许多基因参与组织稳态的维持，例如c-myc癌蛋白，它是细胞增殖的重要调节因子，以及Bcl-2蛋白，它参与凋亡的调节。我们回顾性研究了51例葡萄膜黑色素瘤的增殖指标，如有丝分裂计数和Mib-1指数，并将它们的预后意义与已确立的预后指标如细胞类型和肿瘤大小进行比较。同样，我们研究了调节蛋白c-myc和Bcl-2的表达。在所有检测的参数中，最大肿瘤直径和有丝分裂计数与肿瘤相关死亡的相关性最强（分别为P < 0.001和P = 0.005）。此外，细胞类型、上皮样细胞的存在、Mib-1指数和细胞质c-myc阳性细胞百分比是显著的预测因素。多变量分析表明，Mib-1指数、最大肿瘤直径和细胞质c-myc阳性细胞百分比是独立的预后参数。Bcl-2表达与临床结果无关。Mib-1指数与上皮样细胞的存在（P < 0.03）、凋亡小体的存在（P < 0.001）以及c-myc相关。在（细胞核和细胞质）c-myc与Bcl-2之间发现了强烈的负相关关系（分别为P < 0.00004和P < 0.006），这表明Bcl-2与c-myc协同作用使葡萄膜黑色素瘤细胞永生化。
