Martínez-Arribas Fernando, Alvarez Teresa, Del Val Gabriela, Martín-Garabato Elena, Núñez-Villar María-José, Lucas Raul, Sánchez Jaime, Tejerina Armando, Schneider José
Fundación Tejerina-Centro de Patología de la Mama, Madrid, Spain.
Anticancer Res. 2007 Jan-Feb;27(1A):219-22.
Bcl-2 is one of the most important antiapoptotic genes. Although it facilitates the survival of tumor cells, its expression has been consistently associated with a better prognosis for breast cancer. Virtually all studies on Bcl-2 conducted in breast cancer have been carried out by means of immunohistochemistry. The aim of this study was to examine for the first time the expression of Bcl-2 in a series of human breast cancer, both at the mRNA and protein level.
One hundred samples from previously untreated human breast cancers were used; Bcl-2 expression was determined both by means of immunohistochemistry using the bcl-2/100/D5 monoclonal antibody and differential RT-PCR. Additionally, the expression of hormone receptors (ER and PR), c-erb-B2, p53 and the proliferation-associated Ki-67 antigen were also studied by means of immunohistochemistry as part of the standard pathological workup.
Any degree of immunohistochemical staining correlated significantly and inversely with c-erb-B2 expression (p = 0.0008), nuclear grade 3 (p = 0.0015), a Ki-67 labeling index > 10% (p = 0.02) and tumor size (p = 0.048), and in a direct fashion with estrogen (p = 0.0003) and progesterone receptor expression (p = 0.0002). mRNA expression of the Bcl-2 gene showed a significant inverse correlation with c-erb-B2 (p = 0.016) and p53 (p = 0.014) expression, as well as with a nuclear grade 3 (p = 0.006), and a direct correlation with estrogen (p = 0.0004) and progesterone (p = 0.001) receptor expression, as well as with nodal invasion (p = 0.04).
The study of Bcl-2 expression in breast cancer by means of either immunohistochemistry or RT-PCR yields very similar results. In spite of its role opposing tumor cell death, Bcl-2 is associated with biological features of the tumors which define a better intrinsic prognosis, such as hormone receptor expression, low proliferation and absence of c-erb-B2 and mutant p53 expression. This may in great part explain why Bcl-2 expression has been invariably found to correlate with a better prognosis of breast cancer.
Bcl-2是最重要的抗凋亡基因之一。尽管它促进肿瘤细胞存活，但其表达一直与乳腺癌较好的预后相关。几乎所有关于乳腺癌中Bcl-2的研究都是通过免疫组织化学方法进行的。本研究的目的是首次在一系列人类乳腺癌中，从mRNA和蛋白质水平检测Bcl-2的表达。
使用来自未经治疗的人类乳腺癌的100个样本；通过使用bcl-2/100/D5单克隆抗体的免疫组织化学和差异逆转录聚合酶链反应（RT-PCR）来测定Bcl-2的表达。此外，作为标准病理检查的一部分，还通过免疫组织化学研究了激素受体（雌激素受体和孕激素受体）、c-erb-B2、p53以及增殖相关的Ki-67抗原的表达。
任何程度的免疫组织化学染色都与c-erb-B2表达（p = 0.0008）、核分级3级（p = 0.0015）、Ki-67标记指数>10%（p = 0.02）和肿瘤大小（p = 0.048）呈显著负相关，与雌激素（p = 0.0003）和孕激素受体表达（p = 0.0002）呈正相关。Bcl-2基因的mRNA表达与c-erb-B2（p = 0.016）和p53（p = 0.014）表达以及核分级3级（p = 0.006）呈显著负相关，与雌激素（p = 0.0004）和孕激素（p = 0.001）受体表达以及淋巴结浸润（p = 0.04）呈正相关。
通过免疫组织化学或RT-PCR研究乳腺癌中Bcl-2的表达产生非常相似的结果。尽管Bcl-2具有对抗肿瘤细胞死亡的作用，但它与定义更好内在预后的肿瘤生物学特征相关，如激素受体表达、低增殖以及不存在c-erb-B2和突变型p53表达。这在很大程度上可能解释了为什么一直发现Bcl-2表达与乳腺癌较好的预后相关。
