Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues
Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues
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DOI：
10.1002/(sici)1097-0142(20000115)88:2
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发表时间：
2000-01-15
期刊：
影响因子：
6.2
通讯作者：
Gaudin, PB
中科院分区：
文献类型：
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作者：
Chang, SS;Reuter, VE;Gaudin, PB
背景前列腺特异性膜抗原（PSMA）是一种跨膜糖蛋白，在良性前列腺腺分泌腺泡上皮和前列腺癌中高度表达。几项研究的结果表明，在雄激素剥夺的前列腺癌细胞系和雄激素非依赖性肿瘤中，PSMA表达增加。应用抗PSMA单克隆抗体7 E11和PM2J004.5研究了短期雄激素剥夺对前列腺癌组织中PSMA表达的影响。该研究纳入了临床局限性前列腺癌患者，这些患者被前瞻性随机分配至2个治疗组之一：3个月的新辅助雄激素剥夺治疗，随后进行根治性前列腺切除术（ADT/RP）或单纯根治性前列腺切除术（RP）。通过链霉抗生物素蛋白-生物素方法，用抗PSMA mAb 7 E11和PM2J004.5对代表性福尔马林固定、石蜡包埋的前列腺切片进行免疫染色。作者记录了良性上皮、高级别前列腺上皮内瘤（PIN）和前列腺癌中染色的阳性细胞的染色强度和百分比。他们比较了7 E11与PM2J004.5在良性上皮、高级别前列腺和癌中的结果，还比较了两个治疗组之间的结果（ADT/RP vs. RP单独治疗）。两种抗PSMA mAb均染色良性分泌腺泡上皮、高级别PIN和前列腺癌。在两个治疗组中，在良性上皮和前列腺癌中，与7 E11相比，PM2J004.5与显著更大百分比的细胞（P <0.001）和显著更大强度（P < 0.001）反应。使用两种抗PSMA mAb，高级别PIN中染色的细胞百分比和染色强度与前列腺癌中的相似。在单独接受RP的组中，与良性上皮相比，在高级别PIN和前列腺癌中用7 E11染色的细胞百分比和染色强度显著更大（P < 0.001），并且与良性上皮相比，在高级别PIN和前列腺癌中用PM2J004.5染色的强度显著更大（P < 0.001）。ADT/RP组中，前列腺癌中7 E11和PM2J004.5染色的细胞百分比和染色强度均显著高于良性上皮（P < 0.006）。PSMA染色与Gleason评分（在单独接受RIP的组中）或病理分期（在单独接受RP和ADT/RP的组中）均不相关，并且在两个治疗组之间没有差异。短期新辅助ADT不影响良性前列腺分泌腺泡上皮、高级别PIN或前列腺癌中的PSMA表达。前列腺癌和高级别PIN表达的PSMA水平显著高于良性前列腺分泌腺泡上皮。与7 E11相比，PM2J004.5 anti-PSMA mAb是福尔马林固定、石蜡包埋组织中前列腺癌的更敏感的免疫组化标记物。(C)2000美国癌症协会
BACKGROUND. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in benign prostate secretory-acinar epithelium and prostate carcinoma. The results of several studies suggest that PSMA expression is increased in prostate carcinoma cell lines subjected to androgen deprivation and in androgen-independent tumors. The authors studied the effects of short term (3-month) androgen deprivation on PSMA expression in prostate carcinoma specimens using two anti-PSMA monoclonal antibodies (mAbs), 7E11 and PM2J004.5.METHODS. The study included patients with clinically localized prostate carcinoma who were prospectively randomized into 1 of 2 treatment groups: 3 months of neoadjuvant androgen deprivation therapy followed by radical prostatectomy (ADT/RP), or radical prostatectomy (RP) alone. Representative formalin fixed, paraffin embedded prostate sections were immunostained with the anti-PSMA mAbs 7E11 and PM2J004.5 by the streptavidin-biotin method. The authors recorded the staining intensity and the percentage of positive cells stained in benign epithelium, high grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma. They compared the results of 7E11 with those of PM2J004.5 in benign epithelium, high grade prostate, and carcinoma and also compared the results between the two treatment groups (ADT/RP vs. RP alone).RESULTS. Both anti-PSMA mAbs stained benign secretory-acinar epithelium, high grade PIN, and prostate carcinoma. In both treatment groups, PM2J004.5 reacted with a significantly greater percentage of cells (P < 0.001) and with significantly greater intensity (P < 0.001) compared with 7E11 in benign epithelium and prostate carcinoma. With both anti-PSMA mAbs, the percentage of cells stained and the intensity of staining in high grade PIN was similar to that in prostate carcinoma. In the group that received RP alone, the percentage of cells stained and the intensity of staining with 7E11 were significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001), and the intensity of staining with the PM2J004.5 was significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001). In the ADT/RP group, the percentage of cells stained and the intensity of staining with 7E11 and PM2J004.5 were significantly greater in prostate carcinoma compared with benign epithelium (P < 0.006). PSMA staining did not correlate with either Gleason score (in the group that received RIP alone) or pathologic stage (in both the RP-alone and ADT/RP groups) and did not differ between the two treatment groups.CONCLUSIONS. Short term neoadjuvant ADT does not affect PSMA expression in benign prostate secretory-acinar epithelium, high grade PIN, or prostate carcinoma. Prostate carcinoma and high grade PIN express significantly higher levels of PSMA than benign prostate secretory-acinar epithelium. Compared with 7E11, the PM2J004.5 anti-PSMA mAb is a more sensitive immunohistochemical marker of prostate carcinoma in formalin fixed, paraffin embedded tissue. (C) 2000 American Cancer Society.