前列腺癌术后 Gleason 分级与 PSA、P504s、Ki -67蛋白表达相关性分析

目的：探讨前列腺癌 Gleason 分级评分与 PSA、P504s、Ki -67蛋白免疫组化表达的关系。方法：采用免疫组化 SP 法检测45例前列腺癌患者术后石蜡包埋组织中 PSA、P504s、Ki -67的表达，并根据 HE 切片进行 Gleason 分级评分。结果：前列腺癌 Gleason 分值越高，PSA 阳性表达越弱（P ﹤0.05），Ki -67阳性表达越强（P ﹤0.05）；P504s 强表达，与 Gleason 评分无相关性（P ﹥0.05）。结论：PSA 表达越弱、Ki -67表达越强，前列腺癌组织分化程度越差，预后越差。P504s 在前列腺癌中强表达，可应用于诊断，与预后无明显相关性。     

前列腺特异性膜抗原和前列腺特异性抗原表达强度与前列腺癌Gleason评分之间的相关性研究

目的研究前列腺特异性膜抗原(PSMA)和前列腺特异性抗原(PSA)的表达强度与前列腺癌Gleason评分之间的相关性。方法制备抗PSMA膜外段表位的单克隆抗体,应用免疫组织化学方法检测前列腺癌中PSMA的表达,统计分析其与Gleason评分之间的相关性,并和PSA与Gleason评分之间的相关性进行对比。结果制备出8株分泌抗PSMA膜外段表位的单抗的杂交瘤细胞株。免疫组化结果表明,PSMA的表达强度与前列腺癌的Gleason评分之间存在相关性。在分化差的前列腺癌中,PSMA水平高于分化中等和分化良好的前列腺癌(P<0.01),而PSA在前列腺癌中的表达无明显差异(P>0.05)。结论PSMA表达水平在分化差的前列腺癌中明显升高,与Gleason评分存在相关性,可以作为前列腺癌的Gleason分级的标记物,提示PSMA可以作为对激素疗法效果不敏感的低分化前列腺癌抗体介导的免疫治疗靶点。     

丝氨酸/精氨酸富有剪接因子1、核因子κB在前列腺癌中的表达及与患者临床特征的关系

目的探讨前列腺癌组织中丝氨酸/精氨酸富有剪接因子1(SRSF1)、核因子κB(NF-κB)的表达情况及与患者临床特征的关系。方法选取前列腺癌患者和前列腺良性增生患者,各70例,取前列腺癌组织和前列腺良性增生组织。免疫组化法检测前列腺癌组织和前列腺良性增生组织SRSF1、NF-κB蛋白的阳性表达率,并分析不同临床特征前列腺癌患者前列腺癌组织中SRSF1、NF-κB蛋白的表达情况。结果前列腺癌组织中SRSF1、NF-κB蛋白的阳性表达率均高于前列腺良性增生组织,差异均有统计学意义(P﹤0.05)。不同前列腺特异性抗原(PSA)水平前列腺癌患者前列腺癌组织中SRSF1蛋白的阳性表达率比较,差异无统计学意义(P﹥0.05);不同TNM分期、淋巴结转移情况、Gleason评分前列腺癌患者前列腺癌组织中SRSF1蛋白的阳性表达率比较,差异均有统计学意义(P﹤0.05)。不同PSA水平、Gleason评分前列腺癌患者前列腺癌组织中NF-κB蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05);不同TNM分期、淋巴结转移情况前列腺癌患者前列腺癌组织中NF-κB蛋白的阳性表达率比较,差异均有统计学意义(P﹤0.05)。结论前列腺癌组织中的SRSF1、NF-κB蛋白表达水平和阳性表达率均较高,SRSF1蛋白的表达可能与TNM分期、淋巴结转移情况和Gleason评分,NF-κB蛋白的表达可能与TNM分期和淋巴结转移情况有关。     

Prostatic carcinoma: a multivariate analysis of prognostic factors.

Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.     

Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death.

Alpha-methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer relative to benign prostatic tissue. AMACR expression is highest in localized prostate cancer and decreases in metastatic prostate cancer. Herein, we explored the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly. The end points for the cohorts were time to prostate-specific antigen (PSA) failure (i.e., elevation >0.2 ng/mL) and time to prostate cancer death in the watchful waiting cohort. Using a regression tree method, optimal AMACR protein expression cut-points were determined to best differentiate prostate cancer outcome in each of the cohorts separately. Cox proportional hazard models were then employed to examine the effect of the AMACR cut-point on prostate cancer outcome, and adjusted for clinical variables. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006). Among those with both low AMACR expression and high Gleason score, the risk of prostate cancer death was 18-fold higher (P = 0.006). The AMACR cut-point developed using prostate cancer-specific death as the end point predicted PSA failures independent of Gleason score, PSA, and margin status. This is the first study to show that AMACR expression is significantly associated with prostate cancer progression and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer.     

细胞分化抑制子Id1在前列腺癌中的表达及意义

目的:细胞分化抑制子Id1(inhibitor of differentiation or inhibitor of DNA binding)蛋白与肿瘤的发生、侵袭及远处转移有关。本研究主要观测人前列腺癌组织中Id1蛋白的表达,并分析其应用价值。方法:采用免疫组化SP法检测43例前列腺癌(prostate cancer,PC)、12例前列腺增生(benign prostatic hyperplasia,BPH)和2例正常前列腺组织中Id1蛋白的表达。结果:Id1蛋白在正常前列腺组织中无表达;BPH组织中无或弱表达(5/12);所有前列腺癌组织都有阳性表达(43/43),而且大多数以中、高度表达为主(与BPH相比,P<0.01);前列腺癌中Id1的表达水平与Gleason分级成正比(rs=0.63P<0.01)。结论:人前列腺癌组织中,Id1蛋白有过度表达,且与前列腺癌的Gleason分级呈正相关,表明与癌组织的恶性程度有关。Id1蛋白有可能作为判断前列腺癌发展的一种新的肿瘤标志。     

Histopathologic Characterization of Prostate Diseases in Madinah,Saudi Arabia

Aims: To delineate the histopathological pattern of prostate diseases and to highlight age variations in prostatespecific antigen (PSA) values and histopathological features. Materials and Methods: A retrospective reviewwas made of all prostate biopsy reports seen between January 2006 and December 2013 at the King FahadHospital, Madinah, Saudi Arabia. Prostate lesions were tabulated and classified into benign and malignantgroups. Histological scoring of adenocarcinomas was accomplished using the Gleason system. PSA values werecorrelated with Gleason scores. Results: Of 417 prostate lesions reviewed, 343 (82.3%) were benign and 74(17.7%) were malignant, giving a benign to malignant ratio of 4.6:1. Benign prostatic hyperplasia (both with andwithout inflammation) was the commonest prostatic lesion and accounted for 80.3% of all cases and 97.6% of allbenign cases. The age range was 20 to 97 years with a mean of 69.2 years and a peak age group at 70-79 years.Seventy one cases of adenocarcinoma accounted for 95.9% of the total of 74 malignant tumors. It showed an agerange of 44 to 95 years, a mean age of 70.9 years and peak prevalence in the 80-89 year age group. Gleason scoreseven was the most frequent (39.4%) in occurrence. Most adenocarcinomas, 41 cases (57.7%), were moderatelydifferentiated (Gleason score of 5-7). PSA values ranged widely between 16-1,865ng/ml with a mean of 363.4ng/ml.Elevated PSA (>100ng/ml) levels were found in 53 (81.6%) patients. There was a statistically significant positivecorrelation between serum PSA level and Gleason score (p=0.0304). Conclusions: Prostatic lesions constitute asignificant source of morbidity among adult males in Madinah. Benign prostatic hyperplasia was the commonestbenign prostatic lesion and adenocarcinoma was the commonest histological subtype of prostatic cancer.     

前列腺癌组织BSP和PSA的表达及意义

[目的]探讨骨唾液酸蛋白（BSP）与前列腺特异性抗原（PSA）在前列腺癌组织中的表达及意义。[方法]选取不同病理分级的前列腺癌组织（68例）和前列腺增生组织（22例）,采用免疫组织化学SP法染色,检测BSP及PSA的表达情况。[结果]BSP在前列腺癌中阳性率为76.47%,显著高于前列腺增生组织（13.64%）（χ^2=27.614,P〈0.001）。BSP在不同分化程度前列腺癌组织中表达差异无统计学意义（χ^2=0.057,P=0.972）。前列腺增生组织、前列腺癌组织的PSA表达率分别为90.91%、69.12%,差异有统计学意义（χ^2=4.149,P=0.042）。不同分化程度前列腺癌PSA表达差异有统计学意义（χ^2=11.437,P=0.003）。BSP与PSA表达具有显著相关性（rs=0.654,P〈0.001）。[结论]BSP在前列腺癌中高表达,与PSA表达相关。BSP可能在前列腺癌的发生、发展中起重要作用,可能成为前列腺癌治疗的新靶点。     

Predicting prostate specific antigen failure after radical retropubic prostatectomy for T1c prostate cancer

PURPOSE: Clinicopathological data were reviewed to find a predictor of prostate specific antigen (PSA) failure in Taiwanese patients who had received radical retropubic prostatectomy (RRP) for stage T1c prostate cancer (PC). METHODS: Fifty-five consecutive men who underwent RRP for stage T1c PC were included. The clinical end point was PSA failure (PSA >0.2 ng/ml). Preoperative PSA, free-to-total PSA ratio, prostate volume, PSA density, transrectal sextant biopsy and whole mount of RRP parameters were analyzed for their ability to predict postoperative PSA failure. RESULTS: Fifteen of the 55 patients developed PSA failure during the follow-up period. Those with PSA failure had higher PSA, higher percentage of cancer in biopsies and higher biopsy Gleason score than the freedom from PSA failure group (all P < 0.05). The PSA failure group had higher pathology Gleason score and a higher incidence of extracapsular tumor extension than the freedom from PSA failure group (all P < 0.05). The PSA failure group had a larger tumor volume and higher incidence of combined peripheral lobe with transitional lobe involvement than the freedom from PSA failure group (all P < 0.05). Multivariate analysis revealed that the predictors for PSA failure after RRP were biopsy Gleason score > or =6, tumor volume > or =2.5 ml and PSA > or =10 ng/ml. CONCLUSION: The single most significant predictor for PSA failure in T1c PC patients after RRP was tumor volume > or =2.5 ml.     

Preoperative prediction of extracapsular tumor extension at radical retropubic prostatectomy in Taiwanese patients with T1c prostate cancer

BACKGROUND: To find a predictor for extracapsular tumor extension at radical retropubic prostatectomy (RRP) in Taiwanese patients with stage T1c prostate cancer (PC), preoperative transrectal sonoguiding prostate biopsy outcomes and clinicopathological data obtained from these patients were reviewed. METHODS: Fifty-five consecutive men who underwent radical retropubic prostatectomy for stage T1c PC were included. Preoperative sextant needle biopsies of the prostate were performed and whole-mount prostatectomy specimens were processed. The pathological end point was tumor capsular perforation extending entirely through the prostate capsule. Preoperative prostate-specific antigen (PSA), free-to-total PSA ratio, prostate volume, PSA density, Gleason score, number of positive biopsy cores, percentage cancer of sextant biopsies, percentage cancer of one lobe and percentage cancer of one core were analyzed for their ability to predict extracapsular tumor extension at RRP. RESULTS: Eighteen of the 55 specimens showed evidence of tumor capsular perforation. Those with extracapsular tumor extension (ECE) had higher PSA than organ-confined disease (OCD) (18.4 vs 8.3 ng/ml, P < 0.01). The ECE had a higher PSA density than OCD (0.556 vs 0.226, P < 0.01). The percentage of cancer in biopsies, percentage cancer of one lobe and percentage cancer of one core were all higher in ECE than OCD (P < 0.05). The ECE had a higher biopsy Gleason score than OCD (5.6 vs 4.5, P < 0.01). CONCLUSIONS: The four strongest predictors for extracapsular tumor extension of patients with T1c PC were PSA density >or=0.35, biopsy Gleason score >or=6, >or=20% cancer in biopsies and PSA >or=10 ng/ml.     

Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma

BACKGROUND: Pathologic grade and/or histologic score, extraprostatic extension indicated by invasion of the prostatic capsule, margin, and/or seminal vesicles by prostate cancer cells, serum total prostate-specific antigen (PSA), free PSA, complexed PSA levels and/or their ratios, regional pelvic lymph node metastases, and clinical staging have been used to diagnose and monitor the treatment of prostate carcinoma (PC) patients. The Gleason grading system is also used to grade/score a patient's stage of disease, with lower to higher scores indicating progression of PC. However, Gleason's system cannot be used to distinguish biologically aggressive PCs within a single Gleason score. Our objective was to identify subpopulations (or clones) of aggressive prostate cancers within an individual Gleason score by utilizing biological molecule(s) that also facilitate cancer cell invasion to prostatic stroma and metastasis to the lymph nodes. MATERIALS AND METHODS: Specimens were collected from 97 patients with PC and from 8 patients with benign prostatic hyperplasia. These patients had not been treated with hormonal and/or chemotherapeutic agents before undergoing a prostatectomy at the Minneapolis Veterans Affairs Medical Center. Formalin-fixed, paraffin or paraplast-embedded prostate tissue sections were stained with hematoxylin and eosin for pathologic diagnosis and adjacent sections were stained for for immunohistochemical study. We also collected data on age, race, extraprostatic extension, margin status, seminal vesicle, and lymph node invasion by cancer cells, clinical stage at prostatectomy, and mortality/survival data, including the available presurgery and postsurgery serum total PSA and prostatic acid phosphatase concentrations in patients. Immunohistochemical localization of mouse or rabbit anti-cathepsin B (CB) antibody IgG and mouse antihuman stefin (cystatin) A IgG was quantified using a computer-based image analysis system equipped with Metamorph software. RESULTS: CB and stefin A identified aggressive and less aggressive clones of PCs within an individual Gleason score. Tumors with a Gleason Score of 6 that are similar histologically and morphologically were heterogeneous with respect to the ratios of CB to stefin A (CB > stefin A, CB = stefin A, and CB < stefin A). We also found a significant positive association (P = 0.0066) between ratios of CB and stefin A (CB > stefin A) and the incidence of pelvic lymph node metastases, but not with ratios of CB less than stefin A and/or ratios of CB equal to stefin A. Patients with Gleason 7 PCs had a higher incidence of positive lymph nodes than those with Gleason Score 6 tumors. Our data indicated that mortality rates increased in patients when the ratios of CB were greater than stefin A. CONCLUSIONS: PC within an individual Gleason score is a heterogeneous tumor that contains clones or subpopulations of aggressive and less aggressive tumors that can be defined by the ratios of CB to stefin A. PC with an aggressive clone can be identified when the ratio of CB is greater than that of stefin A. Less aggressive clones are identified when the ratio of CB is less than that of stefin A or when the ratio of CB is equal to that of stefin A. The ratios of CB to stefin A can be used in the differential diagnosis and treatment of patients with PC. This is the first report to identify phenotypes of aggressive and less aggressive PCs within a Gleason score.     

Independent prognostic significance of HER-2 oncoprotein expression in pN0 prostate cancer undergoing curative radiotherapy

Existing prognostic algorithms for localized prostate cancer (PC) are hampered by poor validation for endpoints other than biochemical relapse such as clinical disease progression or survival. Therefore, the prognostic relevance of Her-2 (Her-2/neu, c-erbB2) protein expression in patients undergoing curative radiotherapy (RT) was compared to widely accepted prognostic factors such as pretreatment prostate-specific antigen (PSA) levels, biopsy Gleason score and T category of the primary tumor. Biopsies from 112 homogeneously treated patients with T1-4pN0M0 PC were examined by immunohistochemistry and 37% of cases showed membrane-bound Her-2 expression in more than 10% of cancer cells. No definite membrane staining was seen in normal prostate epithelium. With 25 patients dead of PC and a median follow-up of surviving patients of 71 months (range 48-144), the prognostic relevance of Her-2 expression was univariately associated with adverse outcome in terms of biochemical or clinical progression-free survival (B/C-PFS; p = 0.04), clinical progression-free survival (C-PFS; p = 0.02) and disease-specific survival (DSS; p = 0.02). In multivariate analysis, Her-2 expression, T category and Gleason score were independently associated with C-PFS, whereas only Her-2 expression and Gleason score were associated with DSS. Her-2 expression and Gleason score together discriminated 2 groups of patients with 5-year DSS of 95% and 79%, respectively (p < 0.001). Pretreatment PSA levels were associated only with B/C-PFS but not with C-PFS or DSS. Together the data show for the first time that expression of Her-2 is of prognostic relevance in localized PC undergoing RT and suggest that analysis for Her-2 may improve prognostic algorithms for clinically relevant endpoints other than biochemical relapse.     

Significance of MMP-2 expression in prostate cancer: an immunohistochemical study

Prostate cancer is the most common cancer in North American men. Currently available prognostic factors inadequately predict which cancers will be aggressive and which will lead an indolent course. This study was aimed at investigating the role of matrix metalloproteinase (MMP)-2 in prostate cancer disease-free survival. We correlated MMP-2 expression by malignant prostatic epithelium and stromal cells with prostate cancer disease-free survival in 187 stage pT3NxM0 prostate carcinomas using immunohistochemistry. MMP-2 was expressed by cancer cells in 131 cases (70.0%) and by stromal cells in 142 cases (75.9%). MMP-2 expression by stromal cells was not associated with progression (P = 0.7270). However, in multivariate analyses, adjusting for the Gleason score, tumor-node-metastasis stage, and initial serum prostate-specific antigen, MMP-2 expression by >50% of malignant epithelial cells was associated with decreased disease-free survival (hazard ratio, 4.267; P = 0.0012). Increased MMP-2 expression by malignant prostatic epithelia is an independent predictor of decreased prostate cancer disease-free survival.     

Overexpression of HER-2/neu in Patients with Prostatic Adenocarcinoma

Background: Prostatic adenocarcinoma is one of the main causes of cancer death, and its timely diagnosis and preventing its progression dramatically helps improve life indexes. Given the high disease recurrence rate, today, research is more inclined toward exploring causes of recurrence and development, and innovation of modern treatment methods. Several studies have explored over-expression of human epidermal growth factor receptor 2 (HER-2/neu) in prostatic cancer so far, with different results. Thus, it was decided to investigate HER-2/neu overexpression in patients with prostatic adenocarcinoma in Iran. Materials and Methods: A sample size of 40 patients with prostate cancer entered the study, using a cross-sectional, non-randomized sampling method. Parameters studied included patient age at surgery, Gleason score, serum prostatic specific antigen (PSA) before surgery, and positive sample rate after immunohistochemical staining to investigate HER-2/neu overexpression. Results: In terms of HER-2/neu receptor staining rate, of 40 slides, 16 (40%) scored 0, 13 (32.5%) 1+, 7 (17.5%) 2+, and 4 (10%) 3+. In total 27.5% of slides showed HER-2/neu overexpression. In terms of age, an inverse correlation was found (-0.181), but without significance (p=0.263). In terms of serum PSA, the correlation coefficient was 0.449 (p=0.004). With respect to Gleason score, the coefficient was 0.190 (p=0.240). Conclusions: In this study, HER-2/neu overexpression occurred in 27.5% of prostate cancer cases, which is a relatively high figure, compared to similar studies elsewhere. While, we failed to reveal any relationship between HER-2/neu expression status with progression and prognosis of disease, it was demonstrated that the serum PSA level was significantly higher in cases with increased receptor expression.     

Lower levels of nuclear beta-catenin predict for a poorer prognosis in localized prostate cancer

Beta-catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of beta-catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for beta-catenin expression using immunohistochemistry. Nuclear beta-catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear beta-catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse-free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate-specific antigen (PSA) levels (p = 0.01). Analysis of the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear beta-catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear beta-catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear beta-catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear beta-catenin expression may be of clinical utility as a preoperative prognostic marker in low-risk localized PC.     

前列腺癌组织中Kindlin-2和Clusterin蛋白表达及与PSA含量的相关性

目的:探讨前列腺特异性抗原（PSA）含量和前列腺癌（PCA）组织中Clusterin、Kindlin-2蛋白阳性表达的相关性,研究前列腺癌的治疗策略。方法:45例前列腺增生和55例前列腺癌组织应用免疫组织化学方法检测凋亡蛋白Kindlin-2、Clusterin的表达并检测对应病例的血浆PSA含量。结果:Clusterin、Kindlin-2蛋白在前列腺癌组织中的阳性表达率分别为50.9%(28/55)、63.6%(35/55),Clusterin和Kindlin-2蛋白在前列腺增生组织中的阳性表达率分别为0(0/45)、51.1%(23/45)。在前列腺癌和前列腺增生组织中Clusterin和Kindlin-2阳性表达率具有统计学差异(P<0.05);Clusterin和Kindlin-2蛋白表达与前列腺癌病理分级、临床分期、转移情况和PSA含量相关,差异有统计学意义（P<0.05）。结论:联合检测Kindlin-2、Clusterin蛋白和PSA可为前列腺癌提供一种新的联合检查方法。     

HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy

HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1–0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.     

CXCR6 is expressed in human prostate cancer in vivo and is involved in the in vitro invasion of PC3 and LNCap cells

In spite of the clinical importance of prostate cancer (PCa) bone metastasis, the precise mechanisms for the directed migration of malignant cells remain unclear. In the present study, the expression of CXCR6 in human PCa and benign prostatic hyperplasia samples, and the expression of CXCL16 in human osseous tissues were determined by immunohistochemistry. It was found that the level of CXCR6 protein expression was elevated in human malignant prostate tumors, and CXCL16 was expressed positively by human osteocytes in vivo . The in vitro experiments further confirmed that the PCa cell lines PC3 and LNCap expressed CXCR6 at both the mRNA and protein levels, and exogenous CXCL16 has the potential to stimulate the invasion of PC3 and LNCap. To further elucidate the role of the CXCL16–CXCR6 axis in PCa progression, we compared the expression of CXCR6 and CXCR4 in human PCa tissues and the effects of CXCL16 and CXCL12 on the in vitro invasion of PC3 and LNCap cells. It was shown that CXCR6 and CXCR4 proteins were coexpressed and elevated in human PCa samples, and CXCL16 and CXCL12 promoted the invasion of PC3 and LNCap via their respective receptors. Furthermore, in contrast to CXCL12, which enhanced the activity of matrix metalloproteinase (MMP) 9 and MMP2 in PC3 and LNCap, CXCL16 ligation resulted in stronger MMP9 and MMP2 activity in LNCap but not in PC3. Our results suggest that besides CXCL12/CXCR4, CXCL16/CXCR6 might be another important factor involved in PCa bone metastasis. ( Cancer Sci 2008; 99: 1362–1369)     

前列腺腺癌组织中HPV16/18蛋白的表达及意义

 目的 探讨高危型人乳头瘤病毒16/18（HPV16/18）在人体前列腺腺癌组织中的表达及其与临床病理参数的关系。方法 选取86例前列腺腺癌和80例前列腺增生组织标本,通过免疫组织化学Max Vision二步法检测HPV16/18蛋白表达情况。结果 前列腺腺癌组和前列腺增生组的HPV16/18阳性表达率分别为22.58%和11.25%,差异有统计学意义（P=0.018）。在前列腺腺癌组内,HPV16/18的表达与Gleason评分和临床分期有一定的关系,差异有统计学意义（均P<0.05）,而与患者PSA水平、有无脉管侵犯、有无淋巴结转移和有无远处转移关系不大,差异无统计学意义（均P>0.05）。结论 HPV16/18与前列腺腺癌的发生发展有一定的关系,有可能成为前列腺腺癌早诊早治的生物学指标之一。     

High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results

PURPOSE: To present the long-term outcome and morbidity of high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) for localized prostate cancer. METHODS AND MATERIALS: Between September 1991 and December 1998, 209 consecutive patients with no prior androgen suppression were treated with HDR-BT plus EBRT. The median follow-up was 7.25 years (range, 5-12 years). The patients were stratified into three risk groups: low (Stage T2a or less, Gleason score 20). Four definitions of PSA progression were compared with the general clinical failure outcome: the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, nadir plus 2.0 ng/mL, two consecutive rises >/=0.5 ng/mL, and PSA level >0.2 ng/mL. Morbidity was scored using Radiation Therapy Oncology Group criteria. RESULTS: The general clinical control rate was 90% (188 of 209), and the general clinical failure rate was 10% (21 of 209). The overall survival rate was 79%, and the cause-specific survival rate was 97%. The PSA progression-free survival (ASTRO definition) rate was 90%, 87%, and 69% for the low-, intermediate-, and high-risk groups, respectively. The nadir plus 2 ng/mL and two rises >/=0.5 definitions correlated better with the actual clinical outcome than did the ASTRO and PSA >0.2 ng/mL definitions. The rate of Grade 3 and 4 late urinary morbidity was 6.7% and 1%, respectively, mostly occurring in patients who had undergone post-RT transurethral prostate resection. No late Grade 3 or 4 rectal morbidity developed. The sexual potency preservation rate was 67%. CONCLUSION: Our 10-year results have demonstrated HDR-BT plus EBRT is a proven treatment for all stages of localized prostate cancer. The morbidity was low, but post-RT transurethral resection should be avoided.