Bevilacqua P, Barbareschi M, Verderio P, Boracchi P, Caffo O, Dalla Palma P, Meli S, Weidner N, Gasparini G
St. Bortolo Regional Medical Center, Vicenza, Italy.
Breast Cancer Res Treat. 1995;36(2):205-17. doi: 10.1007/BF00666041.
In the present study we update previous results on the prognostic value of intratumoral microvessel density (IMD), determined immunocytochemically using the monoclonal antibody CD-31 and a standard streptavidin-immunoperoxidase technique, published in the J Clin Oncol 12:454-466, 1994. This study was undertaken in those 211 node-negative breast cancer (NNBC) cases of that series of which we had pathological material available to determine all the prognostic indicators. The median period of follow-up has been extended to 78 and 80 months for relapse-free survival (RFS) and overall survival (OS), respectively, and new biological indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expression) were included in the analysis. The main results obtained are: i) a confirmation that IMD is not associated with the other biological markers studied, i.e. expression of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD was weakly associated only with histological grade (p = 0.053); ii) IMD remains a highly significant prognostic factor for RFS and OS (p < 0.0001 and p = 0.018, respectively) in univariate analysis; iii) in multivariate analysis on RFS, IMD (likelihood ratio test (LRT) = 30.16; p < 0.0001), 67 kDa laminin receptor (LRT = 9.80; p = 0.0017), the IMD/67 kDa laminin receptor interaction (LRT = 8.62; p = 0.0033), tumor size (LRT = 8.56; p = 0.0034), and p53 protein (LRT = 4.96; p = 0.025) are significant and independent prognostic indicators. For OS, only tumor size (LRT = 8.34; p = 0.0038), menopausal status (LRT = 5.16; p = 0.023), p53 protein (LRT = 4.37; p = 0.036), and IMD (LRT = 4.05; p = 0.044) retain a significant and independent prognostic value. The results of this study confirm the prognostic importance on RFS of the variables previously tested, but not of peritumoral lymphatic vessel invasion. A novel finding is that 67 kDa laminin receptor and the IMD/67 kDa laminin receptor interaction are also significant and independent variables. For OS, the results confirm that both IMD and tumor size are significant and independent variables. With prolonged follow-up the novel finding that emerges is the prognostic importance of menopausal status and p53 protein. This new information could be useful for a more accurate selection of high-risk NNBC patients who require careful follow-up and may benefit from adjuvant therapy.
在本研究中，我们更新了先前关于瘤内微血管密度（IMD）预后价值的结果。该结果于1994年发表在《临床肿瘤学杂志》第12卷第454 - 466页，当时是采用单克隆抗体CD - 31和标准链霉亲和素 - 免疫过氧化物酶技术通过免疫细胞化学方法测定IMD。本研究针对该系列中211例淋巴结阴性乳腺癌（NNBC）病例开展，我们拥有这些病例的病理材料，可用于确定所有预后指标。无病生存期（RFS）和总生存期（OS）的中位随访期分别延长至78个月和80个月，并且分析中纳入了新的生物学指标（即Ki - 67标记和67 kDa层粘连蛋白受体表达）。获得的主要结果如下：i）证实IMD与所研究的其他生物学标志物无关，即p53蛋白、c - erbB - 2蛋白、67 kDa层粘连蛋白受体的表达以及细胞动力学；IMD仅与组织学分级呈弱相关（p = 0.053）；ii）在单因素分析中，IMD仍然是RFS和OS的高度显著预后因素（分别为p < 0.0001和p = 0.018）；iii）在RFS的多因素分析中，IMD（似然比检验（LRT）= 30.16；p < 0.0001）、67 kDa层粘连蛋白受体（LRT = 9.80；p = 0.0017）、IMD/67 kDa层粘连蛋白受体相互作用（LRT = 8.62；p = 0.0033）、肿瘤大小（LRT = 8.56；p = 0.0034）和p53蛋白（LRT = 4.96；p = 0.025）是显著且独立的预后指标。对于OS，只有肿瘤大小（LRT = 8.34；p = 0.0038）、绝经状态（LRT = 5.16；p = 0.023）、p53蛋白（LRT = 4.37；p = 0.036）和IMD（LRT = 4.05；p = 0.044）保留显著且独立预后价值。本研究结果证实了先前检测的变量对RFS的预后重要性，但未证实瘤周淋巴管侵犯的预后重要性。一个新发现是67 kDa层粘连蛋白受体以及IMD/67 kDa层粘连蛋白受体相互作用也是显著且独立的变量。对于OS，结果证实IMD和肿瘤大小都是显著且独立的变量。随着随访时间延长，出现的新发现是绝经状态和p53蛋白的预后重要性。这些新信息可能有助于更准确地选择需要密切随访且可能从辅助治疗中获益的高危NNBC患者。
