Bostwick David G, Qian Junqi, Maihle Nita J
Bostwick Laboratories, Richmond, Virginia 23294, USA.
Prostate. 2004 Feb 1;58(2):164-8. doi: 10.1002/pros.10322.
Amphiregulin (AMP) is a heparin-binding glycoprotein that is structurally and functionally related to epidermal growth factor. Its effects are mediated by the tyrosine kinase activity of the epidermal growth factor receptor (EGF-R), and specific nuclear targeting sequences. AMP induces cell proliferation after androgen stimulation of human prostate cancer cell lines. An autocrine proliferative loop involving AMP, androgen, and EGF-R may, therefore, play a role in prostatic carcinogenesis. The purpose of this study was to compare the expression of AMP in benign prostatic epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma.
We performed an immunohistochemical study of select sections from 93 radical prostatectomies performed at the Mayo Clinic between 1987 and 1991. All patients were previously untreated and found to have pathologic stage T2N0M0 adenocarcinoma after routine handling of surgical specimens. Affinity-purified polyclonal antibody directed against AMP was applied to tissue sections using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in 10% increments. Intensity on a scale from 0 (negative) to 3 (strongly immunoreactive) and pattern of expression (nuclear versus cytoplasmic) also were recorded.
AMP immunoreactivity was present in benign prostatic epithelium, PIN, and prostatic adenocarcinoma in all cases. The mean percentage of AMP-immunoreactive cells was 53.8% in benign epithelium, 65.9% in PIN, and 74.3% in cancer. Intensity was moderate in all cases. The pattern of expression was usually nuclear in benign epithelium (secretory and basal cells), and usually cytoplasmic or nuclear and cytoplasmic in PIN and adenocarcinoma. There were rare scattered immunoreactive cells in the stroma, ejaculatory duct epithelium, and urethral urothelium. Endothelial cells were invariably unstained.
AMP expression in prostate increases progressively from benign epithelium to PIN and cancer. Increased expression of AMP may contribute to the development of prostatic adenocarcinoma. Predominantly nuclear staining was observed in benign epithelium, whereas cytoplasmic or nuclear and cytoplasmic staining was observed in PIN and adenocarcinoma. The differences in nuclear and cytoplasmic localization of immunoreactivity may reflect the presence of two pathways of activation, and hence varying biological functions of AMP.
双调蛋白（AMP）是一种肝素结合糖蛋白，在结构和功能上与表皮生长因子相关。其作用由表皮生长因子受体（EGF-R）的酪氨酸激酶活性及特定的核靶向序列介导。在雄激素刺激人前列腺癌细胞系后，AMP可诱导细胞增殖。因此，涉及AMP、雄激素和EGF-R的自分泌增殖环可能在前列腺癌发生过程中起作用。本研究的目的是比较AMP在良性前列腺上皮、高级别前列腺上皮内瘤变（PIN）和腺癌中的表达情况。
我们对1987年至1991年间在梅奥诊所进行的93例根治性前列腺切除术的选定切片进行了免疫组织化学研究。所有患者此前均未接受过治疗，在对手术标本进行常规处理后发现患有病理分期为T2N0M0的腺癌。使用链霉亲和素-生物素法将针对AMP的亲和纯化多克隆抗体应用于组织切片。对于每个病例，以10%的增量估计良性上皮、PIN和腺癌中免疫反应性细胞的百分比。还记录了0（阴性）至3（强免疫反应性）的强度以及表达模式（核型与胞质型）。
在所有病例中，良性前列腺上皮、PIN和前列腺腺癌中均存在AMP免疫反应性。AMP免疫反应性细胞的平均百分比在良性上皮中为53.8%，在PIN中为65.9%，在癌症中为74.3%。所有病例中的强度均为中等。表达模式在良性上皮（分泌细胞和基底细胞）中通常为核型，在PIN和腺癌中通常为胞质型或核质混合型。在基质、射精管上皮和尿道尿路上皮中有罕见的散在免疫反应性细胞。内皮细胞始终不着色。
前列腺中AMP的表达从良性上皮到PIN再到癌症逐渐增加。AMP表达的增加可能有助于前列腺腺癌的发生。在良性上皮中观察到主要为核染色，而在PIN和腺癌中观察到胞质或核质染色。免疫反应性在核和胞质定位上的差异可能反映了两种激活途径的存在，从而表明AMP具有不同的生物学功能。
