van Slooten H J, Clahsen P C, van Dierendonck J H, Duval C, Pallud C, Mandard A M, Delobelle-Deroide A, van de Velde C J, van de Vijver M J
Department of Surgery, Leiden University Hospital, The Netherlands.
Br J Cancer. 1996 Jul;74(1):78-85. doi: 10.1038/bjc.1996.319.
The aim of this study was to assess relationships between Bcl-2 expression, response to chemotherapy and a number of pathological and biological tumour parameters in premenopausal, lymph node-negative breast cancer patients. Expression of Bcl-2 was determined using immunohistochemistry on paraffin-embedded sections in a series of 441 premenopausal, lymph node-negative breast cancers of patients randomised to receive perioperative chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) or no perioperative chemotherapy. Immunohistochemistry of Bcl-2 was evaluated by scoring both staining intensity (0-3) and number of positive cells (0-2). Using these scores tumours were grouped into categories 0-6. It was found that 9.2% of the tumours were completely negative (0), 17.2% weakly (1 + 2), 41.6% moderately (3 + 4) and 31.9% strongly positive (5 + 6) for Bcl-2. A positive correlation was found between high Bcl-2 expression and oestrogen (P < 0.001) and progesterone receptor positivity (P < 0.001) and low tumour grade (P < 0.001), whereas high Bcl-2 expression was negatively correlated with p53 (P < 0.001) and c-erb-B-2 positively (P < 0.001), high Ki-67 index (P < 0.001), mitotic index (P < 0.001) and large tumour size (P = 0.006). Patients with tumours expressing high levels of Bcl-2 (overall score 3-6) had a significantly better disease-free (P = 0.004) and overall (P = 0.009) survival. However, in a multivariate model this association no longer remained significant. There was a trend for an effect of adjuvant chemotherapy on disease-free survival both for patients with Bcl-2-positive (HR-0.61, 95% CI 0.35-1.06, P = 0.07) and negative (HR = 0.55, 95% CI 0.27-1.12, P = 0.09) breast tumours at a median follow-up of 49 months. The level of Bcl-2 expression does not seem to predict response to perioperative chemotherapy in premenopausal, lymph node-negative breast cancer patients. High levels of Bcl-2 are preferentially expressed in well-differentiated tumours and are associated with favourable prognosis. However, Bcl-2 expression is not an independent prognostic factor in this patient series.
本研究旨在评估绝经前、淋巴结阴性乳腺癌患者中Bcl-2表达、化疗反应与一些病理和生物学肿瘤参数之间的关系。采用免疫组织化学方法，对441例随机接受围手术期化疗（5-氟尿嘧啶、阿霉素、环磷酰胺）或不接受围手术期化疗的绝经前、淋巴结阴性乳腺癌患者的石蜡包埋切片进行Bcl-2表达检测。通过对染色强度（0-3分）和阳性细胞数（0-2分）进行评分来评估Bcl-2的免疫组织化学结果。根据这些评分将肿瘤分为0-6类。结果发现，9.2%的肿瘤Bcl-2完全阴性（0分），17.2%弱阳性（1+2分），41.6%中度阳性（3+4分），31.9%强阳性（5+6分）。Bcl-2高表达与雌激素（P<0.001）、孕激素受体阳性（P<0.001）及低肿瘤分级（P<0.001）呈正相关，而Bcl-2高表达与p53（P<0.001）、c-erb-B-2阳性（P<0.001）、高Ki-67指数（P<0.001）、有丝分裂指数（P<0.001）及肿瘤大尺寸（P=0.006）呈负相关。Bcl-2高表达（总评分3-6分）的患者无病生存期（P=0.004）和总生存期（P=0.009）显著更好。然而，在多变量模型中，这种关联不再显著。在中位随访49个月时，辅助化疗对Bcl-2阳性（HR=0.61，95%CI 0.35-1.06，P=0.07）和阴性（HR=0.55，95%CI 0.27-1.12，P=0.09）乳腺癌患者的无病生存期均有影响趋势。Bcl-2表达水平似乎不能预测绝经前、淋巴结阴性乳腺癌患者对围手术期化疗的反应。高水平的Bcl-2优先在高分化肿瘤中表达，并与良好预后相关。然而，在该患者系列中，Bcl-2表达不是一个独立的预后因素。
