前列腺移行带及外周带基质细胞表型特征的研究

目的研究前列腺移行带和外周带基质细胞的表型特征，并比较其差异。方法透射电镜观察3例（年龄分别为21、28和33岁）尸体供者正常前列腺移行带和外周带、3例手术切除的良性前列腺增生（BPH）组织标本移行带基质细胞的超微结构。结果正常移行带间质中富集平滑肌细胞，但大多功能静止，外周带间质分布大量成纤维细胞；成纤维细胞在正常移行带功能旺盛，粗面内质网扩张明显，蛋白合成活跃，而在外周带发生线粒体基质空泡样变性，提示存在功能减退。与移行带相比，外周带平滑肌细胞功能活跃。在增生的移行带中可见大量平滑肌细胞和成纤维细胞，二者功能旺盛，成纤维细胞常聚集成团并形成纤维瘤样结构。结论前列腺基质细胞在移行带和外周带结构间存在差异。BPH组织中，成纤维细胞有向移行带迁移和重新聚集的现象，可能是触发BPH发生在移行带的重要病理基础之一。     

前列腺组织间质细胞的表达及临床意义

目的：研究前列腺增生症（ＢＰＨ）组织间质细胞表达的相关临床意义。方法：应用免疫组织化学和细胞计数方法对前列腺组织各类间质细胞进行定量测定,并与ＢＰＨ患者各项临床参数进行相关分析。结果：ＢＰＨ组织中平滑肌细胞和成纤维细胞明显增多,其中平滑肌细胞数与ＩＰＳＳ呈正相关,与平均尿流率和最大尿流率呈明显负相关,成纤维细胞数与前列腺体积呈明显正相关。结论：平滑肌细胞和成纤维细胞增殖在ＢＰＨ发病过程和临床表现中     

雌二醇促进体外培养的人前列腺平滑肌细胞表型的表达

目的：探讨前列腺增生组织中基质细胞病变的分子机制。方法：建立人前列腺平滑肌细胞（SMC）体外培养技术。SMC在添加雌二醇、相关生长因子和马血清的选择性培养液中培养。采用免疫组织化学方法对SMC和成纤维细胞特异蛋白进行染色,透射电镜观察SMC的超微结构。结果：前列腺SMC在选择性培养液中生长良好;体外培养的SMC在成纤维细胞上呈聚集体生长,形成“山和谷”,SMC特异蛋白呈阳性染色;电镜观察SMC具有微丝、细胞膜凹陷等典型的SMC超微结构。结论：雌二醇能显著促进体外培养的人前列腺SMC表型的表达。     

前列腺增生并发尿潴留膀胱壁病理电镜观察

目的：观察前列腺增生症（ＢＰＨ）并发尿潴留膀胱逼尿肌功能变化。方法：对１０例ＢＰＨ并慢性尿潴留患者实施前列腺摘除术时取膀胱平滑肌组织进行透射电镜观察，同时用１例外伤性膀胱破裂及１例膀胱异物患者的膀胱平滑肌组织作对照。结果：ＢＰＨ并慢性尿潴留患者的膀胱平滑肌显示出下列病变，即平滑肌细胞肥大，排列紊乱，细胞间连接结构减少，其中以胞突连接为主，细胞内线粒体肿胀，胞膜有高电子密度沉积物，脱落细胞胞浆成分散     

肌成纤维细胞与创伤的关系

肌成纤维细胞是一种假定的成纤维细胞的亚型 ,它被认为具有成纤维细胞和平滑肌细胞的某些特征。Ｇａｂｂｉａｎｉ等[1 ] 报道肌成纤维细胞表现出一些平滑肌细胞的超微结构特征 ,包括核褶叠的出现 ,丰富的带有密体的胞质微丝束、复杂的细胞连接 ;同时它还具有丰富的粗面内质网和高尔基体等成纤维细胞的特征 ;肌成纤维细胞出现在皮肤伤口愈合过程中的肉芽组织中 ,对伤口收缩以及细胞外基质成份的堆积起作用[2 ] 。肌成纤维细胞与成纤维细胞不同 ,它的特征是含有α -肌动蛋白同分异构体的张力丝的出现[3] ,而α -肌动蛋白通常在平滑肌细胞中出…     

射频热疗对前列腺组织病理变化和PSA,性激素受体表达的…

为探讨前列腺增生症（ＢＰＨ）射频热疗法机理，对射频热疗前后的人与实验犬前列腺标本，进行了病理组织学，细胞超微结构和前列腺特异抗原（ＰＳＡ）以及睾酮受体（ＡＲ）和雌，孕激素受体（ＥＲ，ＰＲ）表达的动态观察，结果显示，热疗后近期可见前列腺实质水肿，出血，坏死，远期见肉芽组织再生修复，大量纤维组织增生。电镜下见细胞器变性丧失功能，邻近坏死区域组织中可见明显的凋亡，现象。人与犬前列腺标本射频组织ＰＳＡ，Ａ     

性激素受体及相关生长因子在前列腺基质细胞中的表达

目的：探讨前列腺基质增生的发病机制与性激素以及相关生长因子的关系。方法：应用RT－PCR的方法研究了在人前列腺不同细胞类型中Smoothelin的表达，研究了雄、雌激素受体及相关生长因子在前列腺基质细胞中的表达，以及它们在前列腺基质细胞分化中表达的变化。结果：Smoothelin是前列腺平滑肌细胞特异性的标记蛋白；雄激素受体（AR）、碱性成纤维细胞生长因子（bFGF)、角化细胞生长因子（KGF）主要在前列腺成纤维细胞中表达，而雌激素受体（ER）、转移生长因子β1（TGFβ1）主要在平滑肌细胞中表达。结论：前列腺基质增生与雌激素受体和转移生长因子β1的过度表达密切相关。     

组织工程血管模型体外构建的实验研究

目的：在体外环境下，探索构建分别含内皮细胞，平滑肌细胞及成纤维细胞的三层结构的组织工程化血管，三种细胞相互作用，相互支持，形成一个在形态和功能与正常血管近似的组织工程化血管。方法：通过用胶原分别包埋处理的三个管径大小不同，但能相互嵌套的聚羟基乙酸（PGA）管形支架，并种植人脐静脉内皮细胞，人血管平滑肌细胞，人成纤维细胞进行三维立体生长培养，观察细胞生长分化情况。采用酶消化法和组织块法分离培养人脐静脉内皮细胞，人血管平滑肌细胞，人成纤维细胞并传代，纯化，将聚羟基乙酸（PGA）无纺网用胶原溶液包埋，真空冷冻干燥，形成多孔状PGA＋胶原管型支架；接种3代－7代人脐静脉内皮细胞，人血管平滑肌细胞及人成纤维细胞与其内腔面，采用动脉旋转培养技术体外培养3周，行扫描电镜观察。结果：构建后的血管模型，层与层结构紧密，内皮细胞，平滑肌细胞及成纤维细胞分泌细胞外基质，相互进行物质交换，类似于生理条件。结论：该支架具有一定弹性和韧性，在培养液中，能较长时间保持形状。此方法的进一步应用组织工程方法构筑具有分层结构的人造血管打下基础。     

持续恒压扩张和常规间断扩张后皮肤超微结构的改变

目的：对比观察持续恒压扩张（CPTE）和常规间断扩张（CITE）后皮肤组织的超微结构改变。方法：用白色小家猪制作CPTE和CITE动物模型，切取组织样本做电镜观察。结果：CPTE组与正常皮肤和CITE组皮肤比较，皮肤基底细胞和棘细胞间距明显增大，细胞连接明显减少。两实验组扩张后的真皮中，胶原纤维结构基本正常，CPTE组成纤维细胞和血管内皮细胞的活化程度高于CITE组。两实验组中均可见到胶原溶解和成纤维细胞凋亡现象，CPTE组中表现明显。两种扩张方法均可引起毛细血管破裂出血。结论：扩张后皮肤中具有组织生长和退化的双重超微结构改变。     

成纤维细胞生长因子在前列腺中的作用

成纤维细胞生长因于是细胞重要的有丝分裂原，也是形态发生和分化的诱导因子，由７种结构相关多肽生长因子组成的多基因家族。本文综述了成纤维细胞生长因子的生物学特性以及在正常前列腺、前列腺增生症和前列腺癌中的生物学作用。     

bcl-2、Bax和c-myc基因在前列腺增生症中表达的意义

目的 探讨良性前列腺增生症（ＢＰＨ）各区细胞ｂｃｌ－２,Ｂａｘ和ｃ－ｍｙｃ基因表达在ＢＰＨ发病中的意义。方法 对３２例病人的８８份标本采用免疫流式细胞光度术分区检测上述３种基因的标记率和表达量。结果 ｂｃｌ－２基因在周边区（ＰＺ）,移行区（ＴＺ）和中央区（ＣＺ）的标记率分别为１７．５０％,２５．４０％、１７．７０％;ＴＺ明显高于ＰＺ和ＣＺ（Ｐ〈０．０１）,ＰＺ和ＣＺ的标记率相比较差异无显著性（Ｐ〉     

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker

PURPOSE: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer. MATERIALS AND METHODS: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy. DPIV activities were measured by glypro-p-nitroanalide hydrolysis. RESULTS: DPIV activities were significantly higher in TZ than in PZ tissues in men with no evidence of malignancy. However, activities in EPS were negatively associated with TZ volume and positively associated with PZ volume. Mean and median DPIV activities in EPS from men with biopsy determined cancer were significantly higher than in men with no evidence of malignancy. DPIV activities in TZ and PZ biopsies were higher in men with cancer but most markedly in the PZ. CONCLUSIONS: These data indicate that secreted DPIV originates from the TZ and PZ. Increased DPIV activities in cancer are strongly associated with the PZ, which is the zone most commonly involved with cancer. Measuring DPIV levels in expressed EPS or post-digital rectal prostate examination urine may be useful for evaluating men for prostate cancer.     

Does benign prostatic hyperplasia originate from the peripheral zone of the prostate? A preliminary study

OBJECTIVE: To compare the histological characteristics, cell proliferation, apoptosis and biological features in benign prostatic hyperplasia (BPH) in the peripheral (PZ) and transition zone (TZ) of the prostate. PATIENTS AND METHODS: Tissue from BPH in TZ and PZ was obtained from 68 patients undergoing transrectal ultrasonography-guided biopsy and used for both morphometric analysis and immunohistochemical studies. The epithelial, stromal and luminal composition of the tissue was determined using a computer-assisted method for quantitative morphometric analysis. Apoptosis was detected as the apoptotic index (AI) using the TdT dUTP nick-end labelling assay. Cell proliferation was determined as the proliferation index (PI) using Ki-67 immunostaining. The expression of epidermal growth factor receptor (EGFR), transforming growth factor beta1 (TGFbeta1), androgen receptor (AR) and bcl-2 were assessed immunohistochemically. RESULTS: There was no difference in the stroma/epithelium ratio between PZ and TZ hyperplastic nodules (P > 0.05). The mean AI in epithelium was almost identical to the corresponding PI. In stroma, no apoptotic cells were detectable. There was a significantly higher PI and AI in the glandular epithelial cells in PZ hyperplastic than in TZ hyperplastic nodules, but no difference in PI of the stromal cells between PZ and TZ hyperplastic nodules. There was significantly higher expression of TGFbeta1 and lower expression of EGFR and bcl-2 in PZ than TZ hyperplastic nodules (P < 0.05). There was no difference in AR expression between PZ and TZ hyperplastic nodules (P > 0.05). CONCLUSIONS: These results indicate that some hyperplastic nodules in PZ might originate from the PZ, and the formation of these nodules might be modulated in a different way from that in the TZ.     

Is transition zone biopsy valuable in benign prostatic hyperplasia patients with serum prostate-specific antigen >10 ng/ml and prior negative peripheral zone biopsy?

OBJECTIVES: To evaluate the importance of transition zone (TZ) biopsy in benign prostatic hyperplasia (BPH) patients with serum prostate-specific antigen (PSA) >10 ng/ml and prior negative peripheral zone (PZ) biopsy and to estimate the sensitivity of TZ biopsy. MATERIAL AND METHODS: A total of 273 BPH patients with PSA >10 ng/ml and prior negative PZ biopsy underwent an extended biopsy protocol. In patients with a TZ volume <25 cm(3), four TZ biopsies were taken (two cores per side from the apex and base). In patients with a TZ volume > or =25 cm(3) (n=183), six TZ biopsies were taken (three cores per side from the apex, middle and base). Overall, 215 patients were subjected to either transurethral resection of the prostate (n=162) or open enucleation of the adenoma (n=53). RESULTS: The extended biopsy revealed prostate cancers in 21.2% of cases (58/273). The zonal distribution of the positive cores was as follow: PZ cancers only in 67.2% of cases (39/58), TZ cancers only in 13.8% (8/58) and PZ+TZ cancers in 19% (11/58). Overall, 73.6% (14/19) and 36.8% (7/19) of TZ cancers were detected at the apex and middle of the TZ, respectively, while no TZ cancers at all were detected at the base (p=0.00015). The incidence of carcinoma on definitive pathology was 5.6% (12/215). Consequently, TZ biopsy detected only 61.3% (19/31) of TZ cancers. The incidence of pure TZ cancers was 7.3%. On the chi(2) test, patient age, serum PSA, transrectal ultrasonography findings and PSA density did not correlate significantly with the detection rate of TZ cancer. Prostate volume (p=0.023), TZ volume (p=0.027) and PSA/TZ density (p=0.007) were predictive of TZ cancers. CONCLUSIONS: Although TZ biopsy was the sole site of cancer in only 2.9% of cases (8/273), it improved the cancer detection rate by 14% in this selected group of patients. The majority (74%) of TZ cancers were detected at the apex site. TZ biopsy has a low sensitivity (61%).     

Effects of age,sex steroids,and family relationships on volumes of prostate zones in men with and without prostate cancer

Benign prostatic hyperplasia (BPH) and prostate cancer commonly occur together. This suggests that common familial, hormonal, and environmental factors contribute to their development. In men at risk for the development of prostate cancer (at 40 men in 19 families) and aged-matched unrelated controls (n = 46), we have determined whether familial factors, age, and blood hormone concentrations are related to the transition zone (TZ), peripheral zone (PZ), or total volume of the prostate measured by transrectal ultrasound (TRUS). We determined that the influences of age, prostate cancer (n = 15), and familial status did not significantly affect the relationships reported. Therefore, data from all groups were combined for this study. TZ correlated positively with age (P = 0.003) after controlling for family status, but total prostate volume correlated insignificantly with age (P = 0.08). In addition, the ratio of TZ to PZ volumes also correlated significantly with age in the control group (r = 0.27, P = 0.014). Both TZ and PZ volumes correlated highly (r = 0.91, P < 0.0001, n = 86) with total volume. In addition, total volume correlated significantly (r = 0.71, P < 0.001) with the ratio of the TZ/PZ volumes, which also correlated significantly with each other (r = 0.61, P < 0.0001, n = 86). In contrast to the increase of TZ volume related to total prostate volume, PZ volume declined compared with total volume. Prostate volumes up to 50 ml are predominated by the PZ and above 50 ml by the TZ, which may compress and shrink the PZ. Both TZ and total prostate volume correlated positively with serum estrone concentrations (P = 0.04 and P = 0.003, respectively). These results suggest that the risk of prostate cancer does not contribute to generalized overgrowth of the prostate, including the TZ. However, estrogens and age strongly influence TZ but not PZ volume. Both PZ and TZ volumes rise together until the prostate exceeds 50 ml, when the growth of the TZ appears to exceed the PZ and then to compress it.     

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.     

Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones

BACKGROUND: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin. METHODS: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification. RESULTS: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers. CONCLUSIONS: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.     

Clinicopathological study of prostate cancer patients who had a serum PSA level of more than 20 ng/ml and were treated by a radical prostatectomy

PURPOSE: In order to assess the validity of radical prostatectomy for the prostate cancer with PSA greater than 20 ng/ml, we reviewed the clinicopathological characteristics and prognoses of radical prostatectomy cases with PSA greater than 20 ng/ml. MATERIAL AND METHODS: Twenty-one radical prostatectomy cases who had a serum PSA level greater than 20 ng/ml were reviewed regarding their clinicopathological characteristics. Step-sectioned specimens were used for pathological evaluation. RESULT: The serum PSA level ranged from 21 to 65 ng/ml (median : 27 ng/ml). As for the clinical stage, there were 8 T1c cases, 5 T2b cases, 5 T2c cases, and 3 T3a cases (2001. TNM classification). According to the tumor location, 10 cases were diagnosed as peripheral zone (PZ) cancer, and 10 cases were diagnosed as transition zone (TZ) cancer. One case had several small cancer foci both in PZ area and TZ area. In 10 PZ cancer cases, 2 cases had lymph node metastasis, and 8 had seminal vesicle invasion. All of 10 PZ cancer cases showed extraprostatic extension, and 7 showed positive surgical margin. On the other hands in 10 TZ cancer cases, no cases had lymph node metastasis and seminal vesicle invasion. Five TZ cancer cases showed extraprostatic extension, and 6 showed positive surgical margin. The findings of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) were positive in all PZ cancer cases, but these findings were unclear in TZ cancer cases. In addition, no significant difference were observed between the PZ cancer cases and the TZ cancer cases regarding age, PSA, prostate volume, PSA density, cancer volume, and Gleason scores. PSA failure was observed in 9 PZ cancer cases, and 2 TZ cancer cases. CONCLUSION: Based on our findings, the prognosis of TZ cancer cases was better than that of PZ cancer cases among the radical prostatectomy cases with PSA greater than 20 ng/ml. Radical prostatectomy might be one of the effective treatment option for TZ cancer even if the PSA shows greater than 20 ng/ml. It seems to be important to detect TZ cancer properly based on DRE and TRUS findings.     

Significance of routine transition zone biopsies in Japanese men undergoing transrectal ultrasound-guided prostate biopsies

BACKGROUND: The objective of this study was to evaluate the clinical significance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)-guided systematic 8-core peripheral zone (PZ) biopsies. METHODS: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS-guided systematic biopsy of the prostate for the fi rst time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens. RESULTS: Prostate cancer was detected by 10-core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed significantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone. CONCLUSIONS: Routine TZ biopsy did not significantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy.