The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer
The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer
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DOI：
10.1158/1078-0432.ccr-05-1445
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发表时间：
2006-01-01
影响因子：
11.5
通讯作者：
Bartlett, JMS
中科院分区：
文献类型：
--
作者：
Edwards, J;Traynor, P;Bartlett, JMS
目的：I型受体酪氨酸激酶（HER）家族在前列腺癌进展中的作用存在争议。乳腺癌研究表明，这些受体应作为一个家庭进行调查。目前的研究调查了HER 1-HER 4和EGFRvIII在匹配的化疗敏感性和化疗难治性前列腺肿瘤中的表达。实验设计：免疫组织化学分析用于调查HER 1-HER 4、EGFRvIII和磷酸化Akt（pAkt）在匹配的化疗敏感性和化疗难治性前列腺肿瘤中的蛋白表达。令人惊讶的是，HER 2膜在化疗敏感性肿瘤中的高表达与生化复发时间的增加有关。（P = 0.0003），这意味着更长的总生存期（P = 0.0021）。与其他研究一致，HER 4膜表达在化疗敏感性肿瘤中与较长的生化复发时间相关（P = 0.042），EGFRvIII膜表达与较短的生化复发时间相关（P = 0.015）。pAkt表达的增加与存活率降低相关（P = 0.0098）。多变量分析显示，HER 2是前列腺敏感性肿瘤复发时间的独立阳性预测标志物（P = 0.014）。相反，HER 2在难治性肿瘤中的高表达与从生化复发到死亡的时间缩短相关。（P = 0.039），EGFRvIII核表达与生化复发至死亡时间缩短和总生存期缩短相关（P = 0.02和P = 0.005）。结论：这些结果表明HER家族在前列腺癌中可能具有多种作用，并且单独的蛋白质表达不足以预测它们可能引起的生物反应。
Purpose: The role of the type I receptor tyrosine kinase (HER) family in progression of prostate cancer is controversial. Breast cancer studies show that these receptors should be investigated as a family. The current study investigates expression of HER1-HER4 and EGFRvIII in matched hormone-sensitive and hormone-refractory prostate tumors.Experimental Design: Immunohistochemical analysis was used to investigate protein expression of HER1-HER4, EGFRvIII, and phosphorylated Akt (pAkt) in matched hormone-sensitive and hormone-refractory prostate tumors.Results: Surprisingly, high HER2 membrane expression in hormone-sensitive tumors was associated with an increased time to biochemical relapse (P = 0.0003), and this translated into longer overall survival (P = 0.0021). Consistent with other studies, HER4 membrane expression in hormone-sensitive tumors was associated with longer time to biochemical relapse (P = 0.042), and EGFRvIII membrane expression was associated with shorter time to biochemical relapse (P = 0.015). An increase in pAkt expression was associated with reduced survival (P = 0.0098). Multivariate analysis showed that HER2 was an independent positive predictive marker of time to relapse in hormone-sensitive prostate tumors (P = 0.014). In contrast, high HER2 expression in hormone-refractory tumors was associated with decreased time to death from biochemical relapse (P = 0.039), and EGFRvIII nuclear expression was associated with decreased time to death from biochemical relapse and decreased overall survival (P = 0.02 and P = 0.005).Conclusion: These results suggest that the HER family may have multiple roles in prostate cancer, and that expression of the proteins alone is insufficient to predict the biological response that they may elicit.