Ets-1在前列腺癌组织中的表达及其临床意义

目的 探讨原癌基因Ets-1在前列腺组织中的表达及其与前列腺癌组织学分级的关系.方法 利用免疫组化法检测Ets-1在4例正常前列腺组织,12例良性前列腺增生组织和53例前列腺癌组织中的表达.结果 Ets-1蛋白的阳性表达在前列腺癌细胞的胞浆及胞核内均可见,79%的前列腺癌组织中Ets-1呈阳性表达,而在良性前列腺组织细胞中无表达或仅有微弱表达,差异有显著性意义(P<0.05).在前列腺癌组织中,Gleason评分高危组Ets-1阳性表达率明显高于Gleason中危组和低危组(P<0.05).结论 与良性前列腺组织对照相比,Ets-1有肿瘤特异性,其表达与前列腺癌的组织学分级相关,可作为前列腺癌病变程度及临床预后判断的一个分子标志.     

前列腺癌中survivin蛋白的表达

目的检测survivin蛋白在前列腺癌组织中的表达,并分析其与病理分级、临床分期的关系。方法采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结法（S-P法）检测45例前列腺癌、50例前列腺增生组织中survivin蛋白的表达。结果Survivin蛋白在前列腺癌组织中表达率为82．2％（37／45）,其表达率在Gleason评分高分组中明显高于低分组（P〈0．01）,表达强度与Gleason评分呈强正相关,而在不同临床分期中表达率无显著性差异。结论Survivin在前列腺癌组织中的表达与survivin前列腺癌恶性程度密切相关,survivin可能在前列腺癌的进展中起重要作用。     

前列腺癌Gleason分级系统的现代观点

前列腺癌Gleason分级与生物学行为和预后有良好的关联性,已逐渐成为前列腺癌最重要的分级标准,并成为制订治疗方案的重要参考指标。但病理学家们在具体应用、各级别准确划分上还有不同意见。现就前列腺癌Gleason分级目前情况作一综述。     

白细胞分化抗原74在前列腺癌中的表达

目的:探讨白细胞抗原CD74在前列腺癌(PCa)中的表达及临床意义。方法:选择56例PCa和55例癌旁良性前列腺增生(BPH)组织,采用免疫组化染色法观察CD74在上皮细胞及间质细胞中的表达。结果:CD74在PCa和癌旁BPH的上皮细胞及间质中的阳性表达率分别为48.2%、87.3%和62.7%、83.6%,差异有统计学意义(P<0.05或P<0.01);CD74在Gleason评分≤7和>7的PCa间质中的表达率分别是44.0%和80.8%,差异有统计学意义(P<0.05),在Gleason评分≤7分和>7分PCa上皮中阳性率分别为36.7%和61.5%,差异无统计学意义(P>0.05);CD74在低分化PCa浸润部的癌细胞及周围间质中高表达。结论:CD74可能在PCa的发生及侵袭中发挥重要作用,能否成为PCa预后预测指标,仍需积累大量病例继续探讨。     

穿刺标本Gleason评分预测前列腺癌分级的准确性评价

目的　探讨前列腺穿刺标本Gleason评分预测前列腺癌分级准确性的价值及影响因素。　方法　对 45例临床局限性前列腺癌患者前列腺穿刺标本与根治术标本Gleason评分一致性进行比较 ,并对影响一致性的可能因素进行相关分析。　结果　 45例穿刺标本与根治术标本Gleason评分相符者 19例 (42 % ) ;评分偏低 2 2例 (49% ) ,其中偏低 1分 10例 (2 2 % ) ,偏低 >2分 12例 (2 7% ) ;评分偏高 4例 (9% )。二者具有一致性 ,但一致性稍差 (K =0 .3 4 2 ,P <0 .0 1)。偏差与患者年龄、前列腺体积、TPSA、穿刺阳性针数比例、分级及病理分期均无显著相关性 (P >0 .0 5)。前列腺穿刺阳性针数比例在精囊浸润和非浸润组差异有显著性意义 (P <0 .0 5) ,尤其在Gleason评分 >7分时差别有非常显著性意义 (P <0 .0 1)。　结论　穿刺标本Gleason评分结合临床其他资料能有效地指导临床治疗。结合前列腺穿刺阳性针数比例 ,高Gleason评分是筛选前列腺癌精囊浸润病例的有效指标     

survivin蛋白在前列腺癌中的表达及其与肿瘤细胞凋亡的关系

目的 :探讨新的凋亡基因survivin蛋白在前列腺癌 (PCa)的表达及其与肿瘤细胞凋亡的关系。　方法 :采用免疫组化SP法和DNA原位未端标记TUNEL法分别测定 4 2例PCa组织及 10正常前列腺 (NP)组织中survivin蛋白的表达和细胞凋亡。　结果 :survivin蛋白在PCa中的阳性表达为 80 .5 9% ,与病理分级、临床分期和淋巴结转移密切相关 (P <0 .0 5 ) ,而NP中无阳性表达 ;PCa组织及NP组织中细胞凋亡指数 (AI)分别为 3.0 3± 1.33、1.0 7± 0 .77,其差异有显著意义 (P <0 .0 5 ) ;survivin蛋白的表达与细胞AI呈负相关 (r=- 0 .6 79,P <0 .0 0 1)。　结论 :survivin蛋白的异常表达而引起的细胞凋亡抑制 ,在PCa的发生、发展中起一定的作用 ;联合检测survivin蛋白和AI,有助于对肿瘤细胞的分化程度作出正确评价 ,以指导临床治疗及估计预后     

血清PSA及PSA密度与前列腺癌分级分期的关系

目的：提高前列腺癌（PCa）的诊断水平。方法：回顾了60例经穿刺活检确诊PCa患者的临床资料。结果：60例PCa患者中,血清T—PSA含量、F-PSA含量、F／T分别与PCaGleason分级、临床分期均呈正相关,F／T与PCaGleason分级、临床分期均无显著相关。结论：PCa患者的血清T—PSA、F—PSA和PSAD与Gleason分级和临床分期存在相关,提示可能通过检测血清T—PSA、F-PsA和PSAD预测PCa恶性程度及预后,有利于PCa的筛查及制定合理的治疗方案。     

346例前列腺癌的Gleason评分分布特征及其与临床分期的关系

目的:探讨前列腺癌患者G leason评分分布特征及其与临床分期的关系。方法:收集我院1992年1月~2005年6月346例前列腺癌病例资料,建立临床资料数据库,对病理切片进行G leason评分。将病例按不同年份分成3组:1992~1999年、2000~2002年和2003年~2005年6月。采用χ2检验分析G leason评分分布及各组间差异,采用Spearm an等级相关分析,分析前列腺癌G leason评分与临床分期的关系。结果:3组间G leason评分分布差异有显著性(χ2=17.703,P<0.01),G leason评分平均值稍有降低,G leason评分5~7分前列腺癌比例增加(χ2=10.736,P<0.01),临床意义较大的G leason评分7、8、9、10分作为一组,其比例无显著变化(χ2=4.038,P>0.05)。346例前列腺癌中,G leason评分2~6分预测局限性前列腺癌与G leason评分7分和8~10分差异有显著性(χ2=8.786,P<0.01,χ2=22.956,P<0.01),G leason评分7分和8~10分预测局限性前列腺癌差异无显著性(χ2=0.787,P>0.05)。G leason评分与临床分期相关(r=0.452,P<0.01)。结论:G leason评分7分与G leason评分8~10分在预测肿瘤进展方面具有相似效应。G leason评分与临床分期有关,提示其可能是判断前列腺癌预后的一个有意义的指标。     

前列腺癌神经生长因子受体TrkA/p75NTR比值与临床分期、分级的关系

目的:探讨神经生长因子(NGF)的两种受体(Trk A和p75NTR)在前列腺癌(PCa)发生、发展中的表达规律及作用机制。方法:采用免疫组化法研究62例PCa和35例良性前列腺增生(BPH)组织中Trk A及p75NTR蛋白的表达,并结合临床资料进行统计分析。结果:通过成组t检验,发现自BPH组织至低分化PCa组织(Gleason 8~10分),随着组织分化逐渐降低或临床分期逐渐增高,Trk A受体表达显著增强,p75NTR受体表达显著减低,Trk A/p75NTR比例显著增大。在BPH组织中两者比例为0.32,在Gleason评分6分的PCa组织中为0.52,在7分的组织中为1.65,而在8~10分的组织中为5.75;在p T2期组织中两者比例为0.89,在p T3a期为1.5,在p T3b期为3.75,在有淋巴结转移(p Tx N1)的组织中为7.00。结论:Trk A/p75NTR比例的失调性增高,可能是前列腺细胞恶变后的基本特征之一。Trk A/p75NTR比值越高,组织分化程度越低,临床分级、分期越高,患者预后可能越差。     

融合基因TMPRSS2:ERG与前列腺癌病理分级关系的研究

目的:研究融合基因TMPRSS2:ERG和前列腺癌病理分级的关系。方法:选取前列腺癌的穿刺标本62例为病例组,同时选择10例良性前列腺增生(BPH)患者为对照组,同时纳入9株前列腺癌细胞株作为对照,采用巢式RT-PCR检测融合基因TMPRSS2:ERG,比较融合基因阳性和阴性患者Gleason评分的差异,Logistic回归法分析TMPRSS2:ERG和前列腺癌病理特征的关系。结果:62例前列腺癌患者中有28例检测出TMPRSS2:ERG融合基因,阳性率为45.16%;10例BPH和9株癌细胞株中均未检测出该融合基因。融合基因TMPRSS2:ERG阳性和阴性患者Gleason评分无显著差异(Z=-0.609,P=0.542),但融合基因阳性患者Gleason主评分显著高于阴性患者(Z=-2.600,P=0.009)。单因素Logistic回归分析显示,筛状结构、泡沫状腺体和印戒癌细胞分别与融合基因TMPRSS2:ERG有关联(OR=6.25,P=0.002;OR=6.666,P=0.023;OR=3.24,P=0.035);多因素Logistic回归分析显示,该融合基因和筛状结构有关(OR=3.750,P=0.033)。结论:TMPRSS2:ERG融合基因和前列腺癌中到高级的病理分级有关。     

An analysis of radical prostatectomy in advanced stage and high-grade prostate cancer

OBJECTIVES: To clarify the role of radical prostatectomy (RP) in the treatment of locally advanced and high-grade prostate cancer. METHODS: Literature search of Medline publications on surgery for locally advanced and high-grade prostate cancer. RESULTS: In patients with locally advanced disease, the cancer-specific survival rate after RP at 5- and 10-yr follow-up was 85-100% and 57-91.6%, respectively. The overall survival rate at 5 and 10 yr was>75% and 60%, respectively. In patients with high-grade prostate cancer (Gleason score> or =8), the biochemical recurrence-free survival after RP at 5 and 10 yr of follow-up was 51% and 39%, respectively. Nomograms and modern imaging techniques are useful in predicting pathologic stage, presence of positive lymph nodes, or seminal vesicle involvement. These allow physicians to recognise those patients with locally advanced disease who are most likely to benefit from surgical treatment. Downgraded and organ- or specimen-confined high-grade tumours can have a good prognosis after surgery. The prostate-specific antigen value and the percent positive biopsy cores can be helpful in identifying men with high-grade prostate cancer most likely to benefit from RP. CONCLUSIONS: It is likely that surgery has a role in the treatment of locally advanced and high-grade tumours. However, it is necessary and urgent to have randomised trials assessing survival and quality of life when RP is and is not included in the multimodality treatment.     

IMPDH2蛋白与前列腺癌临床相关性分析

【摘要】〓目的〓研究IMPDH2在良性前列腺增生和前列腺癌中的表达,并分析其表达水平与临床病理特征的关系。方法〓收集临床手术切除的前列腺癌组织和前列腺增生,或者穿刺活检组织,所有组织均由病理学确诊。排除已做手术去势的前列腺组织。通过Western Blot检测IMPDH2在前列腺癌、前列腺增生组织中IMPDH2蛋白的表达情况|免疫组化检测前列腺癌、前列腺增生标本中IMPDH2的表达。分析IMPDH2基因的表达水平与临床病理特征的关系。结果〓前列腺癌患者组织中IMPDH2蛋白表达显著上调,IMPDH2蛋白表达上调与肿瘤临床分期、Gleason评分、转移相关。结论 IMPDH2在前列腺癌组织中表达上调,前列腺组织中检测IMPDH2可能有助于判断前列腺癌分化程度并评估预后。     

Gleason score and pretreatment prostate-specific antigen in survival among patients with stage D2 prostate cancer

Although multiple studies have addressed the prognostic importance of tumor differentiation in patients with clinically localized prostate cancer, few data are available in patients with metastatic disease. We evaluated and compared survival data in two groups of men with Whitmore stage D2 metastatic prostate cancer initially treated with hormonal therapy. A series of 76 patients with D2 metastatic disease were evaluated and treated at the National Cancer Institute (NCI) in conjunction with an additional cohort of 141 patients from the Louisiana State University School of Medicine (LSU). Pathological specimens were classified according to the Gleason score. Fifty-two (25%) of the combined NCI/LSU specimens had a Gleason score of 6 or less, 71 (34%) had a value of 7, and remaining 87 (41%) had scores between 8 and 10. The median PSA at the time of diagnosis for the NCI patients was 294.2 ng/ml. Time to treatment failure was defined as the time that a greater than 50% increase above nadir PSA was noted. In neither group was Gleason score correlated with overall survival. There was no association between the time to progression following hormone therapy and primary tumor Gleason score. The PSA concentration at the time of diagnosis was not correlated with the Gleason score for the NCI patients; however, there was an inverse correlation between pretreatment PSA level and time to progression following hormonal ablation. Gleason score does not appear to impact survival in metastatic prostate cancer. PSA as a marker of the biological behavior in metastatic disease may also be limited. These findings should be reevaluated in larger, better matched cohorts. Novel techniques such as serum proteomics, microarrays, and metastatic cell isolation methods may better predict outcome in advanced prostate cancer.     

The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening

OBJECTIVES: The aim of the present study was to evaluate the clinical value of the pretreatment serum testosterone (T) level as a potential predictor of prostate cancer risk in screening for prostate cancer. MATERIALS AND METHODS: The subjects were 420 patients suspected of having prostate cancer who underwent prostate biopsy, and whose pretreatment T levels were recorded. We checked for association between the presence of prostate cancer and the following clinical factors: pretreatment serum T level, age, pretreatment prostate-specific antigen (PSA) level, digital rectal examination findings, ratio of free to total PSA, prostate volume, and PSA density (PSAD). RESULTS: Overall, there was no significant difference in mean pretreatment T level between patients diagnosed with cancer (3.9+/-2.4 ng/ml) and patients diagnosed with benign prostate disease (BPD; 3.7+/-1.7 ng/ml); diagnosis was based on prostate biopsy. However, among patients with PSA <10 ng/ml, the pretreatment T level was significantly higher in patients diagnosed with prostate cancer (4.2+/-2.6 ng/ml) than in patients diagnosed with BPD (3.6+/-1.4 ng/ml) (p=0.007); a similar trend was observed among patients with PSAD <0.15 ng/ml/cc. Multivariate analysis indicated that pretreatment T level was an independent significant predictor of positive prostate biopsy (p=0.020). Additionally, the serum T level was significantly lower in patients with a Gleason score >or=7 (3.7+/-2.1 ng/ml) versus a score <7 (4.2+/-1.7 ng/ml) (p=0.030). Also, serum T levels were significantly higher in well-differentiated prostate cancer (4.8+/-2.1 ng/ml) versus moderately differentiated (3.8+/-1.3 ng/ml) or poorly differentiated (3.7+/-1.4 ng/ml) (p<0.01). CONCLUSIONS: Among relatively low-risk patients, serum T level was an independent significant predictor of positive prostate biopsy, suggesting that the efficiency of prostate cancer screening can be improved by including measurement of serum T level.     

Risk factors associated with perineural invasion in prostate cancer

ObjectivesThe prognostic importance of perineural invasion (PNI) in prostate cancer (PC) has been postulated by some authors. Few studies have investigated the risk factors associated with PNI. The aim of this study was to identify factors associated with PNI in PC.Patients and methodsThe study group of 113 patients diagnosed with PC during the period 2005–2010 consisted of 66 who underwent radical prostatectomy (RP) and 66 who did not. Each group was further divided into those with and without PNI. The association between clinicopathological parameters and PNI in prostate biopsy (Pbx) and RP specimens was investigated using t-test and logistic regression analysis. Discordance in PNI prevalence and PNI up-migration between Pbx and RP specimens were also studied.ResultsIn patients who did not undergo RP, Pbx Gleason score (GS) ≥ 7 was a significant predictor for the presence of PNI. In patients who underwent RP, Pbx GS > 7 increased the risk of PNI in Pbx and RP samples, while a high RP GS predicted PNI in the RP specimen. The discordance rate for PNI in Pbx and RP specimens was 27.3%. Up-migration to a PNI positive cancer between Pbx and RP specimens was seen in 45.5% of cases and RP GS was the only factor associated with PNI up-migration.ConclusionThe association of PNI with a high GS and the high rate of discordance between Pbx and RP specimens indicate that in patients with a high GS on Pbx, the pathologist should look more carefully for PNI, and the surgeon should be aware of sampling errors and the unreliability of Pbx specimens in detecting PNI.     

The face of high risk prostate cancer

OBJECTIVES: To define high risk prostate cancer using prostate cancer specific mortality as the key outcome metric. METHODS: Data from two population based cohorts of men from Connecticut who were diagnosed with localized prostate cancer were analyzed to determine the natural history of prostate cancer and the impact of treatment on long term survival. RESULTS: Men with Gleason 7-10 prostate cancer and a potential survival of 10 years have a high risk of dying from their disease if they elect active surveillance. Surgery appears to offer an improved survival for these men when compared to radiation therapy or observation. Men diagnosed with Gleason 6 tumors in the contemporary era are more likely to harbor low risk prostate cancer when compared to historical series. CONCLUSIONS: Our studies confirm that high risk prostate cancer is best identified by Gleason score 7-10, but challenge the concept that men with high-grade disease are less likely to benefit from radical surgery. Men who have rising PSA values following treatment with either surgery or radiation have residual prostate cancer and are at very high risk of dying from prostate cancer within 10 years.     

血清PSA与前列腺癌病理分级临床分期相关性研究

目的：探讨前列腺癌患者血清PSA与前列腺癌病理分级和临床分期的相关性。方法：前列腺手术前检测PSA，术后经病理检查确诊为前列腺癌患者42例，根据苏木素－伊红染色切片中肿瘤的组织学形态，结合临床资料分别进行病理分级，临床分期，采用Spearman等级相关分析分析PSA与前列腺癌病理分级和临床分期的关系。结果：PSA值与前列腺癌的病理分级有关，与前列腺癌临床分期间的关系目前尚无肯定的结论。结论：PSA值不仅是前列腺癌的一个筛选指标，而且可能是判断前列腺癌预后的一个有意义的指标。     

Comparison of Gleason grade and score between preoperative biopsy and prostatectomy specimens in prostate cancer

AIM: Although the histopathological findings obtained from biopsy specimens are important for choosing the appropriate management of prostate cancer, there have been some discrepancies in Gleason grade and consequently, score between biopsy and surgical specimens. A comparison of findings between these two kinds of specimens was performed. METHODS: Radical prostatectomy was performed at Asahi General Hospital on 223 cases of T1b-T3 without previous cancer treatment, and the Gleason grade and score of the biopsy and surgical specimens were compared. RESULTS: A 37% coincidence in Gleason score was obtained between biopsy and surgical specimens; coincidence including one digit difference in score was approximately 70%. Upgrading was more than downgrading. Disagreement in secondary grade was greater than that in primary grade. Disagreement in Gleason score was roughly similar among different score items and was not influenced by level of prostate-specific antigen, however, the small volume of the cancer tissues more affected the discrepancy in score. CONCLUSION: The use of biopsy findings is required to be taken into account regarding the discrepancy.     

The prognostic significance of Gleason scores in metastatic prostate cancer

PurposeAlthough the majority of metastatic prostate cancer (mPCa) will arise from tumors with Gleason scores (GS) of 8 to 10 existing tumor grade analyses for mPCa have been almost uniformly limited to comparisons of≤7 vs.≥8. In this analysis, we comprehensively evaluate the GS as a prognostic factor for mPCa in the era of the updated Gleason grading system.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with mPCa, GS 6 to 10, diagnosed from 2006 to 2008. GS and primary-secondary Gleason pattern variations were analyzed for overall survival and prostate cancer–specific survival (PCSS).ResultsA total of 4,654 patients were evaluable. At 4 years, the overall survival rates were 51%, 45%, 34%, 25%, and 15% and PCSS rates were 69%, 57%, 44%, 33%, and 21% for GS 6, 7, 8, 9, and 10, respectively. Survival differences for GS 7 vs. 8, 8 vs. 9, and 9 vs. 10 were highly significant on both univariate and multivariate analyses accounting for age, prostate-specific antigen level, and T stage (all P<0.001). Gleason pattern 5 was an independent prognostic factor, both overall for patients with GS 6 to 10 and on primary-secondary Gleason pattern comparisons within the GS 8 (4+4 vs. 3+5 and 5+3) and GS 9 (4+5 vs. 5+4) subgroups. No survival differences were observed between 3+4 vs. 4+3. Overall, lower prostate-specific antigen level, younger age, and lower GS were associated with improved survival, with GS being the strongest prognostic factor for PCSS.ConclusionsIn this large population-based cohort, stratified survival outcomes were observed for GS 6 to 10, with sequential comparisons of GS 7 to 10, and the presence and extent of Gleason pattern 5 representing independent prognostic factors in the metastatic setting.