McCann A H, Dervan P A, O'Regan M, Codd M B, Gullick W J, Tobin B M, Carney D N
Department of Medical Oncology, Mater Misericordiae Hospital, Dublin-7, Ireland.
Cancer Res. 1991 Jun 15;51(12):3296-303.
Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.
我们使用21N多克隆抗体对314例原发性乳腺癌进行免疫组织化学染色，以识别那些过度表达c-erbB-2癌蛋白的肿瘤，并确定这种表达对无病生存期和总生存期的预后意义。这些癌中有52例（17%）出现阳性膜染色，其中7例（13%）为原位导管癌。c-erbB-2阳性与以下因素之间无显著关系：（a）诊断时年龄；（b）绝经状态；（c）肿瘤大小；（d）淋巴结状态；（e）雌激素受体状态；或（f）患者是否有腋窝以外区域的播散性疾病。然而，c-erbB-2阳性肿瘤与较差的分级显著相关（P = 0.02）。这种癌蛋白呈阳性的患者无病生存期较短（P = 0.002），总生存期缩短（P = 0.0001）。这种癌蛋白的过度表达预示着淋巴结阳性疾病（P = 0.003）和Ⅱ级肿瘤患者（P = 0.001）的预后更差。根据雌激素受体状态对患者进行分层显示，与其他亚组相比，c-erbB-2阳性/雌激素受体阴性状态预示着更差的预后（P＜0.001）。314例患者中有42例可获得原发性和复发性肿瘤组织。95%的病例中c-erbB-2表达模式相同，这表明c-erbB-2表达在肿瘤播散过程中没有直接作用。原位导管癌中染色的高发生率表明这种癌蛋白的表达是肿瘤发生的早期事件。最后，多变量分析表明，c-erbB-2癌蛋白是乳腺癌患者总生存期的独立预后指标。
