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血管生成作为接受传统辅助化疗的乳腺癌的预后标志物:多参数及免疫组化分析

Angiogenesis as a prognostic marker in breast carcinoma with conventional adjuvant chemotherapy: a multiparametric and immunohistochemical analysis.

作者信息

Jacquemier J D, Penault-Llorca F M, Bertucci F, Sun Z Z, Houvenaeghel G F, Geneix J A, Puig B D, Bardou V J, Hassoun J A, Birnbaum D, Viens P J

机构信息

Département de Pathologie, Institut Paoli Calmettes, Marseille, France.

出版信息

J Pathol. 1998 Feb;184(2):130-5. doi: 10.1002/(SICI)1096-9896(199802)184:2<130::AID-PATH19>3.0.CO;2-W.

DOI:10.1002/(SICI)1096-9896(199802)184:2<130::AID-PATH19>3.0.CO;2-W
PMID:9602702
Abstract

It has now been clearly established that quantitative immunohistochemical methods applied to tumour angiogenesis under suitable quality control conditions are a powerful prognostic tool for use in the initial assessment of breast carcinomas. Appropriate parameters for predicting the aggressiveness of tumours and their sensitivity to treatment are, however, still required. To determine whether the microvessel count (MVC) may serve to predict the chemotherapeutic response, a retrospective study was carried out on a series of 162 patients with breast carcinoma, who were all treated with the same standard adjuvant chemotherapy. Angiogenesis was assessed by performing CD31 immunostaining and MVC per mm2. Several other factors such as P53, ERBB2, BCL2, and Ki67 were also measured, and their prognostic value was compared with that of the MVC. The MVC was not found to be correlated with any of the other prognostic parameters, but turned out to be of great prognostic value whatever the threshold value chosen, which suggests that it is continuously valid at all levels. The median value of the MVC (43.5 per mm2) divided this series into two significantly different prognostic categories, in terms of both disease-free survival (P = 0.0002) and overall survival (P = 0.037). Univariate analysis showed that most of the parameters analysed were of prognostic value regarding the disease-free survival, namely grade (P = 0.029), mitotic index (P = 0.049), size (P = 0.015), oestrogen receptors (P = 0.022), progesterone receptors (P = 0.018), P53 (P = 0.0045), ERBB2 (P = 0.046), and Ki67 (P = 0.0008). As regards overall survival, grade and ERBB2 showed a loss of prognostic value. In multivariate analysis on disease-free survival, the MVC was the most accurate prognostic factor (RR = 2.64), followed by Ki67 (RR = 2.06) and P53 (RR = 1.69). With respect to overall survival, the MVC ranked third among the prognostic parameters analysed. Standard chemotherapy did not reduce the high prognostic value of the MVC performed on tumour angiogenesis. This suggests that the MVC may predict the degree of resistance to chemotherapy. Patients with high levels of angiogenesis, particularly node-negative patients, might therefore be able to benefit from adjuvant therapy of another kind.

摘要

现已明确证实,在适当的质量控制条件下,应用于肿瘤血管生成的定量免疫组织化学方法是用于乳腺癌初始评估的有力预后工具。然而,仍需要合适的参数来预测肿瘤的侵袭性及其对治疗的敏感性。为了确定微血管计数(MVC)是否可用于预测化疗反应,对162例乳腺癌患者进行了一项回顾性研究,这些患者均接受相同的标准辅助化疗。通过进行CD31免疫染色和每平方毫米的MVC来评估血管生成。还测量了其他几个因素,如P53、ERBB2、BCL2和Ki67,并将它们的预后价值与MVC的预后价值进行比较。未发现MVC与任何其他预后参数相关,但无论选择何种阈值,其预后价值都很大,这表明它在所有水平上都持续有效。MVC的中位数(每平方毫米43.5)将该系列分为两个预后明显不同的类别,无论是无病生存期(P = 0.0002)还是总生存期(P = 0.037)。单因素分析表明,所分析的大多数参数对无病生存期具有预后价值,即分级(P = 0.029)、有丝分裂指数(P = 0.049)、大小(P = 0.015)、雌激素受体(P = 0.022)、孕激素受体(P = 0.018)、P53(P = 0.0045)、ERBB2(P = 0.046)和Ki67(P = 0.0008)。至于总生存期,分级和ERBB2的预后价值丧失。在无病生存期的多因素分析中,MVC是最准确的预后因素(RR = 2.64),其次是Ki67(RR = 2.06)和P53(RR = 1.69)。就总生存期而言,MVC在所分析的预后参数中排名第三。标准化疗并未降低对肿瘤血管生成进行的MVC的高预后价值。这表明MVC可能预测化疗耐药程度。因此,血管生成水平高的患者,尤其是淋巴结阴性患者,可能能够从另一种辅助治疗中获益。

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