Bostwick David G, Qian Junqi, Civantos Francisco, Roehrborn Claus G, Montironi Rodolfo
Bostwick Laboratories, Richmond, VA 23294, USA.
Clin Prostate Cancer. 2004 Mar;2(4):228-35. doi: 10.3816/cgc.2004.n.004.
All forms of androgen-deprivation therapy, including finasteride, induce distinctive histologic changes in benign and neoplastic prostatic epithelial cells, including cytoplasmic clearing, nuclear and nucleolar shrinkage, and chromatin condensation. Treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nucleolar diameter than untreated controls, creating the potential for grading bias. Recognition of these changes may be difficult in needle biopsies and lymph node metastases with treated cancer because of the subtle infiltrative pattern and inconspicuous nucleoli. The effects of finasteride may be less pronounced than other forms of therapy with variable distribution throughout the prostate; further, there may be greater sensitivity of low and intermediate-grade cancer than high-grade cancer. The Gleason grading system for cancer should not be used after finasteride treatment as it is not validated in this setting and is likely to overestimate the biologic potential of high-grade cancer observed after therapy. Chemoprevention trials with agents such as finasteride that alter morphology should not rely on cancer grading as a secondary endpoint owing to grading bias.
包括非那雄胺在内的所有形式的雄激素剥夺疗法,都会在良性和肿瘤性前列腺上皮细胞中引发独特的组织学变化,包括细胞质清亮、核及核仁缩小以及染色质凝聚。与未接受治疗的对照组相比,接受治疗的癌症具有显著更高的结构(Gleason)分级、更低的核分级以及更小的核仁直径,这就产生了分级偏差的可能性。由于治疗后的癌症在针吸活检和淋巴结转移中具有细微的浸润模式且核仁不明显,所以识别这些变化可能会很困难。非那雄胺的作用可能不如其他形式的疗法明显,且在整个前列腺中的分布也不均匀;此外,低级别和中级别的癌症可能比高级别癌症更敏感。非那雄胺治疗后不应使用癌症的Gleason分级系统,因为它在此情况下未经验证,且很可能高估治疗后观察到的高级别癌症的生物学潜能。由于分级偏差,使用非那雄胺等改变形态的药物进行化学预防试验不应将癌症分级作为次要终点。