非那雄胺会改变前列腺病理和癌症分级吗?

David G. Bostwick , Junqi Qian , Francisco Civantos , Claus G. Roehrborn , Rodolfo Montironi
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引用次数: 77

摘要

所有形式的雄激素剥夺治疗,包括非那雄胺,可诱导良性和肿瘤性前列腺上皮细胞发生不同的组织学变化,包括细胞质清除、核和核仁收缩以及染色质凝聚。与未治疗的对照相比,治疗后的癌症具有明显更高的建筑(Gleason)分级,更低的核分级和更小的核仁直径,从而产生分级偏倚的可能性。由于浸润模式和核仁不明显,针刺活检和治疗后的淋巴结转移可能难以识别这些变化。非那雄胺的作用可能不如其他形式的治疗明显,在整个前列腺中分布不一;此外,低、中级别癌症的敏感性可能高于高级别癌症。在非那雄胺治疗后不应该使用Gleason癌症分级系统,因为它没有在这种情况下得到验证,并且可能高估治疗后观察到的高级别癌症的生物学潜力。由于分级偏倚,使用非那雄胺等改变形态的药物进行化学预防试验不应依赖癌症分级作为次要终点。
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Does Finasteride Alter the Pathology of the Prostate and Cancer Grading?

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 highgrade 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.

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