Marks Rebecca A, Zhang Shaobo, Montironi Rodolfo, McCarthy Ryan P, MacLennan Gregory T, Lopez-Beltran Antonio, Jiang Zhong, Zhou Honghong, Zheng Suqin, Davidson Darrell D, Baldridge Lee Ann, Cheng Liang
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Prostate. 2008 Jun 15;68(9):919-23. doi: 10.1002/pros.20715.
The progression of normal prostatic epithelium to androgen-dependent cancer and, eventually, hormone-refractory prostate cancer is a complex process involving many different growth regulatory signals. Activation of epidermal growth factor receptor (EGFR) has been implicated in prostate cancer cell growth.
This study was undertaken to investigate both amplification of EGFR gene by fluorescence in situ hybridization (FISH) and over-expression of EGFR by immunohistochemical staining in prostate tissue from 71 patients treated by hormonal therapy.
EGFR gene amplification was present in 1 of 71 tumors, and polysomy of chromosome 7 was present in 24 of 71 tumors. Immunohistochemically, EGFR expression was demonstrable in 57 of 71 tumors. Membranous immunostaining for EGFR was observed in >75% of tumor cells in 11% of cases, in 51-75% of tumor cells in 20% of cases, in 26-50% of tumor cells in 21% of cases, in 11-25% of tumor cells in 21% of cases, and in 1-10% of tumor cells in 7% of cases. No immunostaining for EGFR was seen in 20% of cases. There was no correlation between EGFR protein expression and gene amplification. There was also no correlation between EGFR expression and clinicopathological characteristics or clinical outcome.
We found that EGFR gene expression was detectable in 35% of this large series of hormone-treated prostate cancer, and that EGFR protein is frequently expressed in tissue from these patients. EGFR over-expression may serve as a reasonable target for therapeutic intervention in this otherwise difficult to treat subset of prostate cancer.
正常前列腺上皮细胞演变为雄激素依赖性癌,最终发展为激素难治性前列腺癌是一个复杂的过程,涉及许多不同的生长调节信号。表皮生长因子受体(EGFR)的激活与前列腺癌细胞的生长有关。
本研究旨在通过荧光原位杂交(FISH)检测71例接受激素治疗患者的前列腺组织中EGFR基因的扩增情况,并通过免疫组织化学染色检测EGFR的过表达情况。
71个肿瘤中有1个存在EGFR基因扩增,71个肿瘤中有24个存在7号染色体多体性。免疫组织化学结果显示,71个肿瘤中有57个可检测到EGFR表达。11%的病例中,>75%的肿瘤细胞出现EGFR膜免疫染色;20%的病例中,51 - 75%的肿瘤细胞出现EGFR膜免疫染色;21%的病例中,26 - 50%的肿瘤细胞出现EGFR膜免疫染色;21%的病例中,11 - 25%的肿瘤细胞出现EGFR膜免疫染色;7%的病例中,1 - 10%的肿瘤细胞出现EGFR膜免疫染色。20%的病例未观察到EGFR免疫染色。EGFR蛋白表达与基因扩增之间无相关性。EGFR表达与临床病理特征或临床结局之间也无相关性。
我们发现,在这一大系列接受激素治疗的前列腺癌中,35%可检测到EGFR基因表达,且这些患者的组织中EGFR蛋白经常表达。EGFR过表达可能是这类难治性前列腺癌治疗干预的合理靶点。