Sierra A, Lloveras B, Castellsagué X, Moreno L, García-Ramirez M, Fabra A
Institut de Recerca Oncològica, Hospital Duran i Reynals, Ciutat Sanitària i Universitaria de Bellvitge, Barcelona, Spain.
Int J Cancer. 1995 Jan 3;60(1):54-60. doi: 10.1002/ijc.2910600108.
The Bcl-2 proto-oncogene product blocks apoptosis. We retrospectively studied Bcl-2 expression in 124 primary tumors from patients diagnosed with T1 (2 cm or less) breast carcinoma with (T1N1) or without (T1N0) lymph-node metastasis. Bcl-2 protein was detected by immunohistochemistry on paraffin-embedded tissue sections. Multivariate logistic regression modeling was used to estimate prevalence odds ratios for lymph-node metastasis. Bcl-2 was widely expressed among T1 tumors showing a strong positive relationship with estrogen (ER)- and progesterone (PR)-receptor-positive tumors. However, a significant inverse correlation was seen between Bcl-2 expression and histological grade, Bcl-2 being absent in the majority of T1 undifferentiated tumors (grade-III carcinomas). Furthermore, Bcl-2 was more frequently expressed in T1N1 cases (72.2%) than in T1N0 specimens (45.7%). The odds for lymph-node metastasis in the Bcl-2-positive group was 3.6 times larger than that in the Bcl-2-negative group. The co-expression of PR significantly modified the effect of Bcl-2 on the odds for lymph-node metastasis, suggesting the existence of a synergistic interaction between the 2 parameters. We studied the percentage of dead cells in primary tumors by in situ DNA fragmentation (FDNA), and found an inverse correlation between Bcl-2 expression and FDNA. This supported the hypothesis that Bcl-2 extends cell survival. In conclusion, our study provides evidence that Bcl-2 expression is involved in breast-cancer progression, at least in a subset of well-differentiated and PR-positive tumors.
Bcl-2原癌基因产物可阻止细胞凋亡。我们回顾性研究了124例经诊断为T1期（2厘米及以下）伴（T1N1）或不伴（T1N0）淋巴结转移的乳腺癌患者原发肿瘤中的Bcl-2表达情况。通过免疫组织化学方法在石蜡包埋组织切片上检测Bcl-2蛋白。采用多因素逻辑回归模型来估计淋巴结转移的患病比值比。Bcl-2在T1期肿瘤中广泛表达，与雌激素（ER）和孕激素（PR）受体阳性肿瘤呈强正相关。然而，Bcl-2表达与组织学分级之间存在显著负相关，在大多数T1期未分化肿瘤（III级癌）中不存在Bcl-2。此外，Bcl-2在T1N1病例（72.2%）中的表达频率高于T1N0标本（45.7%）。Bcl-2阳性组淋巴结转移的几率是Bcl-2阴性组的3.6倍。PR的共表达显著改变了Bcl-2对淋巴结转移几率的影响，表明这两个参数之间存在协同相互作用。我们通过原位DNA片段化（FDNA）研究了原发肿瘤中死亡细胞的百分比，发现Bcl-2表达与FDNA之间存在负相关。这支持了Bcl-2延长细胞存活的假说。总之，我们的研究提供了证据表明Bcl-2表达参与乳腺癌进展，至少在一部分高分化且PR阳性的肿瘤中如此。
