Martínez-Arribas F, Núñez-Villar M J, Lucas A R, Sánchez J, Tejerina A, Schneider J
Fundación Tejerina-Centro de Patología de la Mama, Calle José Abascal 40, 28003 Madrid, Spain.
Anticancer Res. 2003 Jan-Feb;23(1B):565-8.
The balance between the expression of the antiapoptotic gene Bcl-2 and the proapoptotic gene Bax is considered a good indicator of the apoptotic activity of tumor cells. Bcl-2 and Bax expression seem also to individually play a prognostic role in breast cancer. Our aim was to study the expression of both genes in fresh breast cancer samples, and to correlate the obtained results with other available clinical and biological parameters of the tumors.
Fresh tumor specimens from 86 breast cancer patients were studied by means of immunofluorocytometry for the expression of the apoptosis-associated Bcl-2 and Bax genes. Additionally, DNA-ploidy was also measured. Paraffin blocks corresponding to the same tumors were used for immunohistochemistry, to study the expression of hormone receptors (ER and PR), p53, c-erb-B2 and the Ki67 labelling index. Fourteen patients had been treated with four cycles of induction chemotherapy (cyclo-phosphamide, adriamycin and 5-fluorouracil), and separate statistical analyses were carried out both for the whole group, and for the 62 patients not having received any treatment whatsoever, in order to exclude any potential influence of the chemotherapeutic treatment on the expression of the studied antigens.
Bcl-2 expression correlated significantly with estrogen (p = 0.002) and progesterone (p = 0.012) receptor expression, as well as with c-erb-B2 (p = 0.045) expression in chemotherapy-naïve tumors, the correlation being completely lost if treated tumors were added to the study group. A high apoptotic index (Bcl2/Bax < 0.5) correlated significantly with progesterone receptor expression (p = 0.037) and c-erb-B2 expression (p = 0.018), and this correlation was maintained, whether previously treated tumors were included into the study or not (p = 0.038 and p = 0.027, respectively). Bax expression did not correlate with any other clinical or biological parameters of the tumors, including Bcl-2 expression.
Bcl-2 and Bax-expression can be easily determined in clinical breast cancer specimens by means of immunofluorocytometry. Bcl-2-expression significantly correlates with hormone-receptor- and c-erb-B2-expression exclusively in previously untreated tumors. This, however, seems only to be the case when considering Bcl-2 expression in isolation, since a high apoptotic index, which considers the ratio of Bcl-2 versus Bax expression in the same tumor, seems not to be affected by the previous use of chemotherapy.
抗凋亡基因Bcl-2与促凋亡基因Bax表达之间的平衡被认为是肿瘤细胞凋亡活性的良好指标。Bcl-2和Bax的表达似乎也分别在乳腺癌中发挥预后作用。我们的目的是研究这两种基因在新鲜乳腺癌样本中的表达，并将所得结果与肿瘤的其他可用临床和生物学参数相关联。
通过免疫荧光细胞术研究了86例乳腺癌患者的新鲜肿瘤标本中凋亡相关基因Bcl-2和Bax的表达。此外，还测量了DNA倍体。对应于相同肿瘤的石蜡块用于免疫组织化学，以研究激素受体（ER和PR）、p53、c-erb-B2的表达以及Ki67标记指数。14例患者接受了四个周期的诱导化疗（环磷酰胺、阿霉素和5-氟尿嘧啶），对整个组以及62例未接受任何治疗的患者分别进行了统计分析，以排除化疗对所研究抗原表达的任何潜在影响。
在未经化疗的肿瘤中，Bcl-2表达与雌激素（p = 0.002）和孕激素（p = 0.012）受体表达以及c-erb-B2（p = 0.045）表达显著相关，如果将接受治疗的肿瘤加入研究组，则这种相关性完全消失。高凋亡指数（Bcl2/Bax < 0.5）与孕激素受体表达（p = 0.037）和c-erb-B2表达（p = 0.018）显著相关，无论是否将先前接受治疗的肿瘤纳入研究，这种相关性都保持不变（分别为p = 0.038和p = 0.027）。Bax表达与肿瘤的任何其他临床或生物学参数均无相关性，包括Bcl-2表达。
通过免疫荧光细胞术可轻松测定临床乳腺癌标本中的Bcl-2和Bax表达。Bcl-2表达仅在先前未治疗的肿瘤中与激素受体和c-erb-B2表达显著相关。然而，似乎只有在单独考虑Bcl-2表达时才是这种情况，因为考虑同一肿瘤中Bcl-2与Bax表达比值的高凋亡指数似乎不受先前化疗的影响。
