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雄激素非依赖期之前及期间前列腺癌中表皮生长因子受体家族的表达

Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence.

作者信息

Hernes E, Fosså S D, Berner Aa, Otnes B, Nesland J M

机构信息

Department of Clinical Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.

出版信息

Br J Cancer. 2004 Jan 26;90(2):449-54. doi: 10.1038/sj.bjc.6601536.

Abstract

Novel palliative strategies for patients with androgen-independent prostate cancer (AIPC) include targeting the epidermal growth factor receptor (EGFR) family. The aim of the present study was to investigate intrapatient changes of EGFRs during the development of AIPC. In total, 106 symptomatic AIPC patients were identified in whom prostatic biopsies (adenocarcinoma) were available both before the start of androgen deprivation (PRTR biopsy) and after the development of AIPC (AIPC biopsy). All four known subgroups of the EGFR family were determined by immunohistochemistry (IHC): c-erbB-1 (EGFR), c-erbB-2 (HER2/neu), c-erbB-3 (HER3) and c-erbB-4 (HER4). Moderate to strong membrane-specific staining was recorded semiquantitatively (<10% vs >/=10%=IHC stained tumour cells: 'negative' vs 'positive' staining). The medical records were reviewed for clinical variables. During the development of AIPC, intrapatient changes occurred in two opposite directions for each of the four EGFRs: negativity changed to positivity, and vice versa, statistically significant only for the increase of c-erbB-1 expression (P=0.001). The c-erbB-2 expression in the AIPC biopsy was associated with a significantly shorter survival from the time of the AIPC biopsy (P=0.029). Our results support ongoing therapeutic attempts of EGFR inhibition in subgroups of patients with prostate cancer. Further research is needed to understand the function of EGFRs in this malignancy.

摘要

雄激素非依赖性前列腺癌(AIPC)患者的新型姑息治疗策略包括靶向表皮生长因子受体(EGFR)家族。本研究的目的是调查AIPC发展过程中患者体内EGFR的变化。总共确定了106例有症状的AIPC患者,这些患者在雄激素剥夺开始前(PRTR活检)和AIPC发展后(AIPC活检)均有前列腺活检(腺癌)样本。通过免疫组织化学(IHC)检测EGFR家族的所有四个已知亚组:c-erbB-1(EGFR)、c-erbB-2(HER2/neu)、c-erbB-3(HER3)和c-erbB-4(HER4)。对中度至强膜特异性染色进行半定量记录(<10%对≥10%=IHC染色的肿瘤细胞:“阴性”对“阳性”染色)。查阅病历以获取临床变量信息。在AIPC发展过程中,四个EGFR中的每一个在患者体内都朝着两个相反的方向发生变化:阴性变为阳性,反之亦然,只有c-erbB-1表达增加具有统计学意义(P=0.001)。AIPC活检中c-erbB-2的表达与从AIPC活检时起的生存期显著缩短相关(P=0.029)。我们的结果支持对前列腺癌患者亚组进行EGFR抑制的持续治疗尝试。需要进一步研究以了解EGFR在这种恶性肿瘤中的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc96/2410152/a67a479c32b3/90-6601536f1.jpg

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