Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS 66160, USA.
Hum Pathol. 2012 Jan;43(1):23-30. doi: 10.1016/j.humpath.2011.04.011. Epub 2011 Jul 20.
Bcl-2 is a tumorigenic protein that is expressed in 25% to 50% of breast cancers. Although its expression has been widely accepted as a favorable prognostic marker, its protective mechanism of action remains unclear. "Triple-negative" tumors are an aggressive subgroup known to carry a poor prognosis. Studies documenting prognostic significance of Bcl-2 expression in triple-negative in comparison to non-triple-negative breast cancers are limited. Bcl-2 expression was correlated with tumor size, grade, histologic type, lymphovascular invasion, lymph node status, patients' overall survival, estrogen receptor, progesterone receptor, Her-2, p53, and epidermal growth factor receptor in 124 triple-negative and 458 non-triple-negative tumors. There were significant differences between triple-negative and non-triple-negative tumors in their relationship to Bcl-2 expression (81% versus 29%, respectively) and tumor aggression. As previously reported, in non-triple-negative tumors, Bcl-2 positivity correlated with less aggressive tumors (94% of grade I tumors were Bcl-2+ versus 62% of grade III tumors, P < .011) and overall survival (P = .008). However, the opposite was true in patients with triple-negative tumors, where Bcl-2 positivity was associated with poorer survival (P = .64). In triple-negative tumors, Bcl-2 positivity was not associated with any of the aforementioned parameters except for a lower incidence of lymph node metastasis. Moreover, by Cox regression analysis of all variables, in patients with triple-negative tumors, lymphovascular invasion (P = .009) and Bcl-2 expression (P = .028) were predictors of poor survival. In conclusion, there are major clinicopathologic differences between breast cancer phenotypes. Our results establish the value of using Bcl-2 in prognostic stratification of patients and its potential therapeutic implications in selecting patients for treatment.
Bcl-2 是一种致癌蛋白，在 25% 到 50%的乳腺癌中表达。尽管其表达已被广泛接受为有利的预后标志物，但它的保护作用机制仍不清楚。“三阴性”肿瘤是一种侵袭性亚组，预后不良。有研究记录了 Bcl-2 表达在三阴性乳腺癌与非三阴性乳腺癌中的预后意义，但数量有限。在 124 例三阴性和 458 例非三阴性肿瘤中，Bcl-2 的表达与肿瘤大小、分级、组织学类型、脉管侵犯、淋巴结状态、患者总生存、雌激素受体、孕激素受体、Her-2、p53 和表皮生长因子受体相关。三阴性和非三阴性肿瘤在与 Bcl-2 表达的关系（分别为 81%和 29%）和肿瘤侵袭性方面存在显著差异。如前所述，在非三阴性肿瘤中，Bcl-2 阳性与侵袭性较低的肿瘤相关（94%的 I 级肿瘤为 Bcl-2+，而 62%的 III 级肿瘤为 Bcl-2+，P<.011）和总生存（P=.008）。然而，在三阴性肿瘤患者中则相反，Bcl-2 阳性与较差的生存相关（P=.64）。在三阴性肿瘤中，Bcl-2 阳性与除淋巴结转移发生率较低外的上述所有参数均无关。此外，通过对所有变量的 Cox 回归分析，在三阴性肿瘤患者中，脉管侵犯（P=.009）和 Bcl-2 表达（P=.028）是生存不良的预测因素。总之，乳腺癌表型之间存在主要的临床病理差异。我们的研究结果确立了 Bcl-2 在患者预后分层中的价值及其在选择患者进行治疗方面的潜在治疗意义。
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