第一部分  前列腺影像报告数据系统(PI-RADS)及磁共振引导  穿刺对前列腺癌诊断的研究
目的
1. 利用磁共振(MR)引导前列腺靶向穿刺标本，评价多参数磁共振检查(mp-MRI)及前列腺影像报告数据系统(PI-RADS)在中国人群前列腺癌的诊断价值。
2. 比较经直肠超声(TRUS)引导下前列腺系统穿刺与MR引导下前列腺靶向穿刺对前列腺癌诊断的准确性，分析影响前列腺癌诊断的相关因素，为临床诊断前列腺癌提供指导。
方法
1. 回顾性分析2014年7月至2016年3月于我院行前列腺穿刺患者资料，其中213例患者接受TRUS引导下前列腺系统穿刺，同期54例患者行多参数核磁共振检查并接受MR引导下前列腺靶向穿刺活检。对磁共振影像信息及病理资料进行总结，比较2种穿刺方式对前列腺癌诊断的价值。
2. PI-RADS评分由影像科医师严格按照欧洲泌尿放射学会(ESUR)标准对每个兴趣点(ROIs)分别进行评估，分析PI-RADS系统对前列腺癌诊断的敏感性和特异性。
3. 采用SPSS 19.0统计软件，患者年龄、前列腺体积、血清PSA、PI-RADS评分等正态分布资料采用?x±s表示，组间比较采用t检验；计数资料采用率表示，组间比较行χ2检验；临床特征与前列腺癌相关性分析采用Spearman相关性分析；PI-RADS的诊断价值应用ROC曲线评价进行；以P<0.05为差异有统计学意义。
结果
1. 两组患者年龄、前列腺体积及血清前列腺特异性抗原(PSA)无统计学差异(P＞0.05)。所有患者整体诊断阳性率为45.7%，MR穿刺组(50.0%)略高于TRUS组(44.6%)，但不构成统计学差异（P＞0.05）；同时，中高危前列腺癌患者比例MR组(77.8%)高于TRUS组(71.6%)，其两组差异具有统计学意义(P＜0.05)。
2. MR靶向患者共穿刺ROIs 84处，其中前列腺癌29处，前列腺增生55处。患者血清PSA、PSA密度、前列腺体积、病灶最大径与穿刺结果具有相关性(P＜0.05)。
3. 不同病理类型ROIs穿刺前T2WI、DWI、PI-RADS评分具有明显差异，高级别前列腺癌PI-RADS评分明显高于低级别肿瘤，差异有统计学意义(P＜0.05)。
4. 以病理结果为参考行ROC曲线分析，曲线下面积(AUC)分别为0.75、0.85、0.82。以3.5分为界值，T2WI、DWI、PI-RADS对前列腺癌诊断敏感度分别为76%、83%、83%，特异度分别为73%、80%、78%。
结论
1. PI-RADS评分与前列腺癌及其恶性程度具有显著相关性，可以在临床中作为前列腺癌诊断的可靠手段。
2. MR引导前列腺靶向穿刺具有较高的准确性，对中高危前列腺癌诊断率高于TRUS引导前列腺系统穿刺，可在有效诊断高危前列腺癌的同时，在一定程度上减少过度诊断及过度治疗。
 
第二部分  前列腺影像报告数据系统(PI-RADS)与ERG、PTEN表达特点对前列腺癌不良术后病理的评价
目的
1. 进一步评价PI-RADS系统对不同级别前列腺癌的诊断价值。
2. 分析TMPRSS2-ERG基因融合及PTEN缺失在中国人群的突变特点及临床预后价值。
3. 探索接受根治性前列腺切除术患者不良术后病理事件的发生率及其危险因素。
方法
1. 回顾性分析2013年1月至2015年8月于我院行根治性前列腺切除术患者资料，不良病理事件包括患者术后Gleason评分、临床分期的升高及手术切缘阳性。
2. 患者前列腺磁共振信息由影像科医师按照ESUR PI-RADS评价标准(第二版)进行评定(1～5分)，TMPRSS2-ERG基因融合、PTEN缺失、AR、Ki-67表达利用前列腺穿刺标本行免疫组化分析确定。
3. 计数资料采用率表示，组间比较行χ2检验。临床特征与前列腺癌免疫组化相关性分析采用Spearman相关性检验；不良术后病理事件的危险因素分析采用二分类Logistic回归分析。以P<0.05为差异有统计学意义。
结果
1. 共纳入分析病例111例，患者诊断年龄为48～82岁，平均67.76±7.51岁。确诊时血清PSA 2.02～67.87ng/ml。术后病理学分级升高29例（26.1%），病理分期升高9例（8.1%），术后切缘阳性12例（10.8%）；发生不良病理事件患者共37例（33.3%）。
2. 前列腺磁共振影像特点与患者术前血清PSA、临床分期、Gleason评分、穿刺阳性针数、最大肿瘤穿刺长度明显相关。其中T2WI评分与患者临床分期、Gleason评分、穿刺阳性针数呈正相关。不同DWI评分患者穿刺Gleason评分具有显著差异，评分越高，高级别肿瘤风险越大，不同临床分期患者比较无统计学差异。
3. ERG染色阳性仅见于前列腺癌、前列腺上皮内瘤变（PIN）组织，正常前列腺及增生腺体无阳性染色。所有患者阳性表达23例(20.7%)，阴性患者88例(79.3%)。PTEN染色阳性见于正常腺体及间质组织，肿瘤组织染色阳性者共80例(72.1%)，PTEN缺失者31例(27.9%)。随着肿瘤级别的升高，ERG阳性率及PTEN突变率逐步提高，对于Gleason评分≥8分的患者，ERG阳性率达50.0%，PTEN突变率达42.9%，差异具有统计学意义（P＜0.05）；ERG与PTEN状态与患者临床分期无相关性。
4. 血清PSA＞20ng/ml是患者术后分级升高的独立危险因素（OR:18.71, 95%CI:2.05～171.14）；PTEN表达缺失患者，术后切缘阳性风险是正常组23倍（OR:23.02, 95%CI:1.58～336.38）。
结论
1. 前列腺多参数磁共振检查及PI-RADS系统对肿瘤负荷及恶性程度具有较好的预测价值，对临床分期的判断准确可靠。
2. 我国人群ERG基因融合及PTEN缺失的发生率远低于欧美国家。ERG蛋白表达与前列腺癌Gleason评分、Ki-67阳性率密切相关，可用于前列腺癌恶性程度评价及预后分析；PTEN突变在高级别肿瘤及血清PSA＞10ng/ml的患者更为常见。
3. 血清PSA＞20ng/ml、PTEN表达缺失是患者不良术后病理的独立危险因素。

Section 1 Evaluation of the PI-RADS scoring system and MR targeted biopsy for the diagnosis of prostate cancer

Objective

1. To evaluate the efficiency of Prostate Imaging Reporting and Data System（PI-RADS）for the diagnosis of prostate cancer in Chinese population.

2. To compare the efficiency of MR targeted and transrectal ultrasonography guided prostate biopsy for the diagnosis of prostate cancer.

Methods

1. Retrospectively analyze the cases from July 2014 to March 2016, of which, 54 patients accepted MR guided prostate biopsy and 213 patients accepted TRUS guided biopsy. The results of MR imaging and pathologic information were analyzed.

2. The PI-RADS score of each Region of Interests（ROIs） was evaluated according to the European Society of Urological Radiology (ESUR) guideline.

3. Statistical analysis was carried out with the SPSS 19.0 computer package. Comparisons between the normally distributed data were carried out with Student’s t-test．Pearson chi-square test was used to compare between count data. The relationship between clinicopathologic characteristics and prostate cancer was analyzed with Spearman correlation analysis. Receiver operating characteristics (ROC) curve was performed to test diagnostic efficacy of mp-MRI. A P value<0.05 was considered statistically significant．

Results

1. There were no statistical differences between two groups for the patients age, prostate volume and serum PSA(P＜0.05). The overall diagnosis rate for prostate cancer was 45.7%, with a higher rate for the MR targeted group (50.0%) than TRUS group (44.6%)(P＜0.05). More patients with intermediate and high risk prostate cancer were diagnosed by MR targeted biopsy(77.8%) than TRUS guided biopsy(71.6%)(P＜0.05).

2. 84 ROIs in the MR targeted group were evaluated, of wich 29 were prostate cancer and 55 were BPH. Serum PSA, PSA density, prostate volume, maximum cancer core length were related with biopsy results(P＜0.05).

3. Compared with BPH, the PI-RADS score of prostate cancer was higher for T2WI, DWI and PI-RADS and the score of high grade prostate cancer was also higher than that of low grade cancer(P＜0.05).

4. The area under the curve (AUC) for the detection of prostate cancer was 0.75, 0.85 and 0.82 for T2WI, DWI and PI-RADS, with the sensitivity of 76%, 83%, 83% and specificity of 73%, 80%, 78%.

Conclusions

1. The PI-RADS scoring system showed high power to detect prostate cancer, which is of great value for the diagnosis of prostate cancer in Chinese population.

2. The MR targeted biopsy was more sensitive with intermediate and high risk prostate cancer, which is of great value for the prevention of overdiagnosis and overtreatment of prostate cancer.

Section 2 Evaluation of the PI-RADS scoring system and ERG/PTEN status for the prognosis of prostate cancer

Objective

1. To further evaluate the efficiency of Prostate Imaging Reporting and Data System（PI-RADS）for the diagnosis and prognosis of prostate cancer in Chinese population.

2. To analyze the status and prognostic value of TMPRSS2-ERG fusion and PTEN deletion in prostate cancer.

3. To explore the incidence and risk factors of unfavorable pathologic events after radical prostatectomy.

Methods

1. Retrospectively analyze the cases with radical prostatectomy from January 2013 to August 2015. The unfavorable pathologic events includes upstaging, upgrading and positive surgical margin after surgery.

2. The PI-RADS score was evaluated according to the European Society of Urological Radiology (ESUR) guideline. TMPRSS2-ERG gene fusion, PTEN deletion status and AR, Ki-67 expression were detected by immunohistochemical analysis of the biopsy specimen.

3. Comparison between counting data were carried out with Pearson chi-square test. The relationship between clinicopathologic characteristics and prostate cancer was analyzed with Spearman correlation analysis. Risk Analysis of unfavorable pathologic events was performed with logistic regression analysis. A P value<0.05 was considered statistically significant．

Results

1. There were 111 cases analyzed, of which the age ranged from 48 to 82 years, with the median age 67.76±7.51. The serum PSA at diagnosis ranged from 2.02 to 67.87 ng/ml. Upgrading was present in 29 cases (26.1%), and 9(8.1%) for upstaging, 12(10.8%) for positive surgical margins. The overall unfavorable pathologic events were present in 37 cases (33.3%).

2. The PI-RADS score was correlated with serum PSA, clinical staging, Gleason score, number of positive biopsy cores, and maximum cancer core length (P＜0.05). The T2WI score was correlated with clinical staging, Gleason score, and number of positive biopsy cores. Patients with higher DWI score showed higher risk for high grade tumors other than clinical staging.

3. Positive ERG staining was present only in prostate cancer and prostatic intraepithelial neoplasia (PIN), with the overall positive rate being 20.7%. PTEN positive staining showed in all the benign tissue and 72.1% of the tumor tissue. The ERG and PTEN mutation rate were more frequent in patients with higher Gleason score. The ERG positive rate was 50.0% in patients with Gleason score higher than 8, which is 42.9% for PTEN deletion(P＜0.05).

4. Serum PSA＞20ng/ml was independent risk factor for upgrading after surgery, with OR to be 18.71(95%CI: 2.05～171.14), and the risk of positive surgical margins was 23 times higher in patients with PTEN deletion(95%CI:1.58～336.38).

Conclusions

1. Multiparametric MRI and the PI-RADS scoring system were reliable for the clinical staging and risk stratification of prostate cancer in Chinese population.

2. The ERG gene fusion and PTEN deletion rate were much lower than western countries. ERG expression was correlated with Gleason score and Ki-67, which could be used for prognostic evaluation. PTEN deletion was more frequent in patients with serum PSA＞10ng/ml and higher Gleason score.

3. Serum PSA＞20ng/ml and PTEN deletion were independent risk factor for unfavorable pathologic events.