Giai M, Roagna R, Ponzone R, De Bortoli M, Dati C, Sismondi P
Department of Gynecological Oncology, University of Turin, Torino, Italy.
Anticancer Res. 1994 May-Jun;14(3B):1441-50.
The protein product of c-erbB-2 and ras oncogene has been examined for its prognostic potential in both node positive and node negative breast cancer. Using a western blot analysis, levels of these proteins were determined in 159 primary human breast tumor specimens. We examined relationships between gene expression and coexpression with other established markers of prognosis, as well as clinical outcome. Multivariate analysis showed that nodal involvement was the most powerful prognostic factor for predicting overall survival (< 0.000) and disease-free survival (p = 0.001), whereas c-erbB-2 expression was second only to nodal status for predicting overall survival in the whole series (p = 0.05). A separated stepwise analysis was conducted for node negative patients who did not receive any kind of adjuvant treatment and for node positive ones who underwent adjuvant chemo or hormonotherapy. c-erbB-2 expression independently predicted poor survival among node negative tumors (p = 0.001) and was associated with ras expression among node positive cases (p = 0.04). If adjuvant treatment is included in the model, coexpressing tumors are less responsive to Tamoxifen and CMF regimens than those with low levels of protein expression (p = 0.04). These results are potentially of clinical value in separating a subset of node positive breast cancer patients for more intense postsurgical treatment. Among node negative patients, the sole expression of c-erbB-2 enhanced levels, is more likely to retain a predictive value in relation to the response after conventional adjuvant treatment.
已对c-erbB-2和ras癌基因的蛋白质产物在淋巴结阳性和阴性乳腺癌中的预后潜力进行了研究。采用蛋白质印迹分析,测定了159例原发性人类乳腺肿瘤标本中这些蛋白质的水平。我们研究了基因表达以及与其他已确立的预后标志物的共表达与临床结果之间的关系。多变量分析表明,淋巴结受累是预测总生存期(<0.000)和无病生存期(p = 0.001)的最有力预后因素,而在整个系列中,c-erbB-2表达在预测总生存期方面仅次于淋巴结状态(p = 0.05)。对未接受任何辅助治疗的淋巴结阴性患者和接受辅助化疗或激素治疗的淋巴结阳性患者进行了单独的逐步分析。c-erbB-2表达独立预测淋巴结阴性肿瘤患者生存期较差(p = 0.001),且在淋巴结阳性病例中与ras表达相关(p = 0.04)。如果在模型中纳入辅助治疗,与低水平蛋白质表达的肿瘤相比,共表达肿瘤对他莫昔芬和CMF方案的反应较差(p = 0.04)。这些结果对于区分一部分淋巴结阳性乳腺癌患者进行更强化的术后治疗可能具有临床价值。在淋巴结阴性患者中,c-erbB-2表达单独增强,在传统辅助治疗后的反应方面更有可能保留预测价值。