Têtu B, Brisson J
Department of Pathology, Université Laval, L'Hôtel-Dieu de Québec, Canada.
Cancer. 1994 May 1;73(9):2359-65. doi: 10.1002/1097-0142(19940501)73:9<2359::aid-cncr2820730919>3.0.co;2-9.
The influence of HER-2/neu on prognosis of breast cancer is controversial. The authors investigated by immunohistochemistry in node-positive disease the influence of the pattern of immunostaining (membranous or cytoplasmic) on outcome and the prognostic significance of this marker in patients receiving or not receiving adjuvant therapy.
The immunostaining for HER-2/neu oncoprotein was performed on formaldehyde-solution-fixed, paraffin-embedded sections of 888 node-positive breast cancers resected between 1980 and 1986 and for which a follow-up of 2.5-10.5 years was available. The staining was performed using a polyclonal antibody (dilution, 1/15).
One hundred forty-three cases (16.1%) revealed a positive membrane staining with or without additional cytoplasmic contribution, whereas cytoplasmic staining alone was noted in 118 cases (13.3%). Positive membrane staining was correlated with more involved lymph nodes (P = 0.005), aneuploidy (P = 0.002), poor nuclear (P < 0.0001) and histologic (P = 0.007) grades, absence of estrogen (P < 0.0001) and progesterone (P < 0.0001) receptor content, and cathepsin D expression (P = 0.009). No relation was found (P > 0.05) with either age, tumor size, or HSP27 expression. Membrane staining was strongly associated with poor distant metastasis-free or overall survival rate (P < 0.0001), whereas cytoplasmic staining had no prognostic significance. Two hundred thirty-two patients (26.1%) received no additional treatment after surgery. The difference in survival rates between cases with positive and negative staining was only significant among patients submitted to adjuvant chemotherapy or hormone therapy.
This study strongly supports the association of HER-2/neu oncoprotein expression with poor prognosis in node-positive breast cancer and demonstrates that membranous but not cytoplasmic staining is prognostically relevant. It also shows that HER-2/neu oncoprotein expression is useful in predicting survival time only in patients receiving adjuvant therapy, thus suggesting that it may be a marker of drug resistance.
HER-2/neu对乳腺癌预后的影响存在争议。作者通过免疫组织化学方法，研究了淋巴结阳性疾病中免疫染色模式（膜性或胞质）对预后的影响，以及该标志物在接受或未接受辅助治疗患者中的预后意义。
对1980年至1986年间切除的888例淋巴结阳性乳腺癌的甲醛固定、石蜡包埋切片进行HER-2/neu癌蛋白的免疫染色，这些病例有2.5至10.5年的随访资料。使用多克隆抗体（稀释度为1/15）进行染色。
143例（16.1%）显示有阳性膜染色，伴或不伴有额外的胞质染色，而仅胞质染色的有118例（13.3%）。阳性膜染色与更多受累淋巴结（P = 0.005）、非整倍体（P = 0.002）、核分级差（P < 0.0001）和组织学分级差（P = 0.007）、雌激素（P < 0.0001）和孕激素（P < 0.0001）受体含量缺失以及组织蛋白酶D表达（P = 0.009）相关。未发现与年龄、肿瘤大小或HSP27表达有相关性（P > 0.05）。膜染色与远处无转移生存率或总生存率低密切相关（P < 0.0001），而胞质染色无预后意义。232例患者（26.1%）术后未接受额外治疗。阳性和阴性染色病例之间的生存率差异仅在接受辅助化疗或激素治疗的患者中显著。
本研究有力支持了HER-2/neu癌蛋白表达与淋巴结阳性乳腺癌预后不良的关联，并表明膜性而非胞质染色具有预后相关性。研究还表明，HER-2/neu癌蛋白表达仅在接受辅助治疗的患者中对预测生存时间有用，因此提示它可能是耐药的标志物。
