Analysis of distribution of dihydrotestosterone concentration in prostate cancer tissue and differences of dihydrotestosterone and androgen induced gene expression after androgen deprivation

目的：分子研究提示种族对前列腺肿瘤生物学的影响。我们在日本患者中使用组织微阵列（TMA）评估了多种已知的局部前列腺癌预后标志物。方法：选取我院1997 ~ 2001年间接受根治性手术的52例患者标本，标本均未接受新辅助激素治疗，且有3个及以上肿瘤病灶。检测Ki67、p53和雄激素受体（AR）抗原的表达。用前列腺特异性抗原（PSA）监测化疗复发的结果，比较免疫组化评分。结果：病理肿瘤(T)分类（p=0.047）、世界卫生组织（WHO）评分（p=0.026）、WHO组织学分级（p=0.026）、手术切缘状态（p=0.018）是预测生化失败的重要常规临床病理指标。TMA Gleason sum （p=0.038）、TMA primary Gleason grade （p=0.013）、Ki67标记指数（LI） （p<0.0001）、p53 （p=0.0097）、AR （p=0.0113）抗原表达均有显著性差异。此外，手术切缘状态和Ki67 LI与治疗失败独立相关。结论：尤其是ki67li、p53和AR在日本局限性前列腺癌患者中的表达通常可以预测术后进展。

Objectives : Molecular studies suggest that ethnicity influences prostate tumor biology. We evaluated multiple known prognostic markers in localized prostate cancers using tissue microarrays (TMA) in Japanese patients.Methods : Specimens were from 52 patients undergoing radical surgery at our institution between 1997 and 2001 without neoadjuvant hormonal therapy with complete 3 or more available cancer spots. Ki67, p53, and androgen receptor(AR) antigen expression were examined. Immunohistochemical scores were compared with outcomes of chemical relapse as monitored using prostate-specific antigen(PSA).Results : Pathologic tumor (T) classification (p=0.047), World Health Organization(WHO) score (p=0.026), WHO histologic grade (p=0.026), and surgical margin status (p=0.018) were significant conventional clinicopathologic variables for predicting biochemical failure. TMA Gleason sum (p=0.038), TMA primary Gleason grade (p=0.013), Ki67 labeling index (LI) (p<0.0001), p53 (p=0.0097), and AR (p=0.0113) antigen expression also were significant. Moreover, surgical margin status and Ki67 LI were independently associated with treatment failure.Conclusions : Especially together, Ki67 LI and p53 and AR expression in a localized prostate cancer often predicted postoperative progression in Japanese patients.