Suo Zhenhe, Risberg Bjørn, Kalsson Mats G, Willman Kenneth, Tierens Anne, Skovlund Eva, Nesland Jahn M
Department of Pathology, The Norwegian Radium Hospital and Institute for Cancer Research, University of Oslo, Oslo, Norway.
J Pathol. 2002 Jan;196(1):17-25. doi: 10.1002/path.1003.
One hundred patients with breast carcinoma followed for 7-11 years were included in the present study of EGFR family members, using immunohistochemistry and RT-PCR. By immunohistochemistry, 36%, 27%, 26%, and 82% of the tumours were positive for EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. All the immunoreactive tumours were confirmed positive by RT-PCR. Tumour size, histological grade, lymph node status, S-phase fraction, and stage were confirmed to be significantly associated with both disease-free and cancer-specific survival in the present study. Methods of treatment, histological type, and ploidy had no significant effect on survival. Statistical analysis of EGFR family members in these tumours showed a significant association between c-erbB-2 expression and reduced disease-free and cancer-specific survival. c-erbB-4 expression was associated with a more favourable outcome. Co-expression of c-erbB-2 and EGFR was associated with a worse prognosis. c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. In conclusion, c-erbB-2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. However, c-erbB-4 antagonizes the c-erbB-2 effect on clinical course in breast carcinomas. To achieve best results with immunotherapy against the c-erbB-2 receptor, clarifying the status of c-erbB-4 expression may be of significance.
本研究纳入了100例乳腺癌患者，采用免疫组织化学和逆转录聚合酶链反应（RT-PCR）对其进行了7至11年的随访。通过免疫组织化学检测，36%、27%、26%和82%的肿瘤组织中表皮生长因子受体（EGFR）、原癌基因c-erbB-2、原癌基因c-erbB-3和原癌基因c-erbB-4呈阳性。所有免疫反应性肿瘤经RT-PCR证实均为阳性。本研究证实，肿瘤大小、组织学分级、淋巴结状态、S期分数和分期与无病生存期和癌症特异性生存期均显著相关。治疗方法、组织学类型和倍体对生存期无显著影响。对这些肿瘤中EGFR家族成员的统计分析显示，c-erbB-2表达与无病生存期和癌症特异性生存期缩短显著相关。c-erbB-4表达与更有利的预后相关。c-erbB-2和EGFR的共表达与更差的预后相关。然而，c-erbB-4表达对c-erbB-2表达的临床影响具有拮抗作用。总之，乳腺癌中c-erbB-2表达与不良临床病程相关，EGFR表达具有协同作用。然而，c-erbB-4可拮抗c-erbB-2对乳腺癌临床病程的影响。为了通过针对c-erbB-2受体的免疫疗法取得最佳效果，明确c-erbB-4表达状态可能具有重要意义。
