Gago F E, Tello O M, Diblasi A M, Ciocca D R
Italian Hospital of Mendoza, Argentina.
J Steroid Biochem Mol Biol. 1998 Dec;67(5-6):431-7. doi: 10.1016/s0960-0760(98)00140-x.
In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdrl gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan-Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further larger studies (validation set as opposed to the training set used in the present study). Due to the complexity of events in cancer, the evaluation of a combination of prognostic factors should be of value to clinicians to make a more objective estimate of the prognosis of individual breast cancer patients.
在本研究中，我们检查了局部原发性乳腺癌女性患者的活检样本，以研究雌激素受体（ER）和孕激素受体（PR）在评估患者转移概率方面的预后性能，并探讨将临床病理和其他分子参数组合成一个评分是否能提高判别能力。这项前瞻性研究涉及205例患者，中位随访时间为5年。评估的临床病理数据包括：患者年龄；肿瘤大小；腋窝淋巴结受累情况；以及肿瘤分级。最具代表性的肿瘤样本被送至单个实验室，用于对以下分子标志物进行免疫组化评估：ER、PR、增殖细胞核抗原（PCNA）、p53蛋白产物、erbB-2（HER-2/neu）癌蛋白和P170糖蛋白（mdrl基因产物）。19.5%（40/205）的患者出现远处转移（研究终点），这些患者大多同时具有不良、中等和良好的预后因素。无病生存分析程序（Kaplan-Meier法）确定肿瘤大小、腋窝淋巴结受累情况、肿瘤分级、受体状态、PCNA、p53、erbB-2和P170为有用的预后因素。比例风险回归分析（Cox法）按重要性顺序确定erbB-2、肿瘤大小、受体状态、肿瘤分级和PCNA为有用的预后因素。为便于评估预后因素，制定了一个实用且简单的评分系统。高病理评分识别出65%发生远处转移的患者，而57%的转移性疾病患者获得高分子评分。当病理评分与分子评分相结合时，远处转移概率的诊断有显著改善，82%的远处转移患者综合评分升高。该评分系统的验证需要进一步的更大规模研究（与本研究中使用的训练集相对的验证集）。由于癌症事件的复杂性，对多种预后因素进行综合评估对临床医生更客观地估计个体乳腺癌患者的预后应具有价值。
