Gasparini G, Gullick W J, Bevilacqua P, Sainsbury J R, Meli S, Boracchi P, Testolin A, La Malfa G, Pozza F
St Bortolo Regional Hospital, Vicenza-Veneto, Italy.
J Clin Oncol. 1992 May;10(5):686-95. doi: 10.1200/JCO.1992.10.5.686.
A study was undertaken to define the prognostic value of the expression of the c-erbB-2 oncoprotein in a series of breast cancer patients when compared by multivariate analysis with expression of the epidermal growth factor receptor (EGFR), DNA ploidy, and conventional clinicopathologic features.
Prognostic indicators were analyzed in 165 primary breast cancers. The c-erbB-2 oncoprotein was recognized by the polyclonal antibody 21N using an immunocytochemical method. Expression of the EGFR was stated immunocytochemically using the monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded sections using a standard flow-cytometric method.
Overall, 27% of carcinomas had membrane 21N-staining and were classified as c-erbB-2-positive. Overexpression of the c-erbB-2 oncoprotein was poorly associated with EGFR expression and the conventional pathologic features, and it was weakly associated with DNA ploidy and nodal status. Univariate analysis showed that c-erbB-2 expression, nodal status, DNA ploidy, and EGFR provided significant prognostic information concerning 4-year relapse-free survival (RFS) with the odds ratios (ORs) of not relapsing of 2.94, 2.83, 2.34, and 2.20, respectively. Regarding overall survival (OS) at 4 years, only nodal status and DNA ploidy had prognostic significance, with the ORs of not dying of 2.68 and 2.80, respectively. Applying multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and DNA ploidy (full model) failed to retain prognostic value (P = .202), whereas nodal status was the most significant indicator of relapse (P = .027) followed by DNA ploidy (P = .056) and EGFR (P = .093).
This study suggests that overexpression of the c-erbB-2 oncoprotein appears to be an important indicator of relapse in stage I-II breast cancer when singly evaluated. Multivariate analysis shows that the determination both of nodal status and DNA ploidy improves our ability to identify subsets of patients with different prognoses, and allows for a better selection of patients for systemic adjuvant treatments.
开展一项研究以确定在一系列乳腺癌患者中，与表皮生长因子受体（EGFR）表达、DNA倍体及传统临床病理特征进行多因素分析比较时，c-erbB-2癌蛋白表达的预后价值。
对165例原发性乳腺癌的预后指标进行分析。采用免疫细胞化学方法，用多克隆抗体21N识别c-erbB-2癌蛋白。使用单克隆抗体EGFR1通过免疫细胞化学方法检测EGFR的表达。采用标准流式细胞术方法在石蜡包埋切片中评估DNA倍体。
总体而言，27%的癌组织有膜21N染色，被归类为c-erbB-2阳性。c-erbB-2癌蛋白的过表达与EGFR表达及传统病理特征相关性较差，与DNA倍体及淋巴结状态相关性较弱。单因素分析显示，c-erbB-2表达、淋巴结状态、DNA倍体及EGFR为4年无复发生存率（RFS）提供了显著的预后信息，不复发的优势比（OR）分别为2.94、2.83、2.34和2.20。关于4年总生存率（OS），只有淋巴结状态和DNA倍体具有预后意义，不死的OR分别为2.68和2.80。对RFS进行多因素分析时，在对淋巴结状态、EGFR和DNA倍体进行校正后（完整模型），21N未能保留预后价值（P = 0.202），而淋巴结状态是复发的最显著指标（P = 0.027），其次是DNA倍体（P = 0.056）和EGFR（P = 0.093）。
本研究表明，单独评估时，c-erbB-2癌蛋白的过表达似乎是I-II期乳腺癌复发的重要指标。多因素分析显示，确定淋巴结状态和DNA倍体可提高我们识别不同预后患者亚组的能力，并有助于更好地选择适合全身辅助治疗的患者。
