前列腺组织中PTTG的表达及其意义

目的：研究垂体肿瘤转化基因（PTTG）在前列腺组织，尤其是前列腺癌组织中的表达及临床意义。方法：采用免疫组织化学二步法检测正常前列腺（8例）、BPH（16例）、无远处转移的前列腺癌（47例）以及有远处转移的前列腺癌（19例）组织中PTTG的表达情况。用Stata统计软件分别对BPH和前列腺癌组织中PTTG的表达情况与PSA和Gleason分级间的关系进行分析。结果：PTTG在正常前列腺和BPH组织中无表达或弱表达，而63．7％（42／66）的前列腺癌中有阳性或强阳性表达，在良恶性前列腺组织之间的表达差异有统计学意义（x2=25．2487，P=0．000），无远处转移的前列腺癌和有远处转移的前列腺癌之间的表达差异无统计学意义（x2=0．3568，P=0．837）。PTTG在前列腺癌中的表达与PSA和Gleason分级之间无相关性。结论：PTTG在前列腺癌组织中高表达，可能在前列腺癌的发生发展过程中起重要作用。     

前列腺组织端粒酶活性检测对前列腺癌的诊断价值

目的 通过检测前列腺穿刺组织端粒酶活性,探讨其在前列腺癌诊断和预后中的临床价值。方法 ２０例前列腺癌标本和１６例癌旁组织均来自前列腺穿刺活检,１４例良隆前列腺增生（ＢＰＨ）标本取自前列腺摘除手术,均经病理证实。采用改良的ＴＲＡＰ－银染方法检测端粒酶活性,并进行半定量分析。结果 ２０例前列腺癌标本中１８例测得端粒酶活性。１６例前列腺癌旁组织中,７例前列腺上皮内瘤（ＰＩＮ）,２例癌旁ＢＰＨ组织有端粒酶     

The role of transrectal aspiration biopsy in the diagnosis of prostatic cancer

We reviewed our experience with transrectal aspiration biopsy during an 18-month period. This procedure was the sole technique used in 75 men and prostatic cancer was diagnosed in 19. Two of these patients were not treated because a core biopsy performed at another hospital was negative for carcinoma. Aspiration and transperineal core biopsies were performed in 62 other cases. The sensitivity of aspiration to diagnose prostatic cancer was 98 per cent (45 of 46 biopsies) compared to only 81 per cent (37 of 46) for the core biopsy method. No patient suffered a complication following the aspiration biopsy. These data further support the value of transrectal aspiration biopsy as a sensitive, easy to perform method for sampling an abnormal prostate. More widespread use of this technique in the United States should be encouraged.     

Cytologic diagnosis of prostatic carcinoma by transrectal prostatic aspiration biopsy

Since October 1982, 500 cases of transrectal fine needle aspiration biopsy have been done. Among them, 486 cases (97.2%) got prostate epithelium enough for diagnosis but 14 cases (2.8%) failed. The cytologic results showed prostatic cancer in 100 cases (20.5%), bladder cancer with metastasis to prostate in 7 cases (1.4%), suspicious cancer in 4 cases (0.82%), hyperplasia of prostate 251 cases (51.64%), normal prostate 104 cases (21.3%), tuberculosis one case (0.2%), lithiasis one case (0.2%), purulent prostatitis 4 cases (0.82%), granulomatous prostatitis 6 cases (1.23%), and insufficient epithelium for diagnosis in 8 cases (1.64%). In this series, there were one false positive and two false negative by Franzen's technique. Among 41 cases received further treatment, 35 prostate specimen were available for regular pathological study. The consistent rate between pathological and cytologic diagnosis was 85.4%. In a word, transrectal prostatic aspiration is an outstanding safe and practical method for the diagnosis of prostate cancer.     

Diagnosis and staging of prostatic cancer by transrectal ultrasonography. A preliminary study.

Sixty men (7 normal, 53 with prostatic disease) underwent transrectal ultrasonic scanning of their prostates in order to assess the technique and evaluate its reliability in the detection and staging of prostatic cancer. The prostatic capsule was clearly seen in 58 men; non-integrity of the capsule occurred only in those with proven cancer (17 cases). An ultrasound diagnosis of cancer was made for 32 of 33 men with proven disease and it was shown that ultrasound demonstrated anterior perforations of the capsule in 6 out of 18 men with tumours that had been judged by rectal palpation to have been confined to the prostate. It is concluded that transrectal ultrasound is a promising technique of imaging the prostate, particularly in relation to selection of patients for biopsy and for checking staging of cancer carried out by digital assessment of the prostate.     

Clinical evaluation of serum basic fetoprotein for prostatic cancer--comparative study with PAP, gamma-Sm and PSA]

The clinical significance of serum basic fetoprotein (BFP) in prostatic cancer was investigated together with serum prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA). Investigated in this study were 40 patients with prostatic cancer, ranging in age from 50 to 85 years (mean age: 69.5 years). According to clinical staging, 3 cases (7.5%) had a stage A disease, 10 cases (25.0%) a stage B disease, 7 cases (17.5%) a stage C disease, and 20 cases (50.0%) a stage D disease. The positive rates for serum BFP, PAP, gamma-Sm, and PSA were 60.0, 45.0, 63.6, and 68.4%, respectively, and these rates increased as the stage advanced. The above results suggest that BFP is the most useful marker of the four for monitoring prostatic cancer. In a combination assay of these four markers, 29 (87.9%) of 33 patients with prostatic cancer could be diagnosed by observing an elevated serum level in one of the markers. This suggests that a combination assay of BFP, PAP, gamma-Sm and PSA in patients with prostatic cancer is useful for diagnosis and monitoring of the disease.     

P53,Rb抑癌基因突变产物在前列腺癌中的表达

用Ｐ５３和Ｒｂ，通过免疫金－银染色方法，对３０例前列腺癌及２０例前列腺增生症进行检测。结果显示：前列腺癌Ｐ５３、Ｒｂｃ１５的阳性率分别为６０．０％和５０％，前列腺增生症仅有１０％和１５％，二者之间有显著性差异。前列腺正常组织阳性率Ｐ５３ 和Ｒｂ为０，与肿瘤区比较Ｐ＜０．００１；３０例前列腺癌中，有１０例Ｐ５３和Ｒｂ同为阳性，Ｐ５３在低分化和未分化癌中阳性表达明显高于高分化腺癌（Ｐ＜０．０１）。     

A decrease in 1H nuclear magnetic resonance spectroscopically determined citrate in human seminal fluid accompanies the development of prostate adenocarcinoma

PURPOSE: Because human prostatic fluid contributes almost 50% of the volume of seminal plasma and this fluid contains unique prostatic metabolites such as citrate, which are markedly altered during tumorigenesis, we investigated high resolution H nuclear magnetic resonance (NMR) spectroscopy of unprocessed human seminal plasma as a rapid, noninvasive diagnostic tool for prostate adenocarcinoma. MATERIALS AND METHODS: Semen and prostatic massage samples from control and tumor bearing subjects were stored frozen at -20C and thawed prior to water suppressed NMR analysis. We found that freezing produced no significant alterations in the semen NMR spectra. Quantitative NMR spectroscopy was performed by first calibrating the water suppression data acquisition sequence with a series of standard samples containing known amounts of citrate within the physiological range. RESULTS: Well resolved citrate resonances from the seminal plasma of 3 control subjects with prostate specific antigen (PSA) less than 1 ng/ml were integrated to give concentrations of 97 to 178 mM. Semen from a 47-year-old man with benign prostatic hyperplasia and a PSA of 5.5 ng/ml contained 156 mM citrate. In contrast, seminal plasma from 2 patients with prostate cancer, including a 46-year-old man with Gleason grade 8 and PSA 45.2 ng/ml, and a 64-year-old man with grade 6 and PSA 13.0 ng/ml, revealed citrate NMR signals corresponding to a concentration of only 28 and 24 mM, respectively. Spectra from prostatic massage fluid from a normal 23-year-old volunteer showed a citrate of 483 mM, while massage fluid from a 56-year-old patient with Gleason grade 4 cancer showed a citrate of only 1.35 mM. CONCLUSIONS: To our knowledge this study is the first to use high resolution NMR of semen to diagnose prostate cancer. Given the known effects of adenocarcinoma on prostate metabolism, the study indicates that high resolution H NMR can be used to measure citrate in seminal fluid, potentially providing a new, rapid, noninvasive screening method.     

Prostate antigen: A new potential marker for prostatic cancer

A prostate-specific antigen, distinct from acid phosphatase, was identified by immunologic procedures in prostate tissues (normal, benign hypertrophic, and cancerous) and seminal plasma, as well as in sera of patients with prostatic cancer and of nude mice bearing human prostatic tumor. This antigen was shown by immunoperoxidase staining to be confined to epithelial cells comprising the prostatic ductal elements. Prostate antigen was purified from prostatic tissue and seminal plasma, and it was shown to have a molecular weight of 33,000-34,000 with no subunit component. The isolectric point of purified antigen was around 6.9, though several unpurified isomers with different isoelec-tric points also were observed. Serum-borne prostate antigen showed a molecular weight of 90,000-100,000, but it exhibited a molecular weight of 36,000 in the presence of sodium dodecyl sulfate. A sandwich-type, peroxidase-linked immunosorbent assay capable of detecting 0.1ng of the antigen per milliliter of blood was developed. With this technique, serum level of the antigen was found to increase in patients with prostatic cancer as compared with normal males. The prostate-specific antigen can be a useful marker for detection of prostatic cancer.     

Assessment of prostatic weight by means of computed tomography and urethroscopy

Preoperative determination of prostatic weight in patients with prostatic hyperplasia is important in determining the choice of the surgical technique used. Prostatic volume determination with CT scans, using the ellipsoid formula, appears to be quite accurate. CT scanning of the prostate gland was performed in 34 patients with prostatic hyperplasia (2 cases with cancer). All scans were performed with a Toshiba TCT-60A-30 scanner, and were made for 10 mm slices as follows. From the CT image the maximum transverse diameter (a) sagittal diameter (b), and the maximum transverse area (S) were easily determined. The long axis was calculated from the bladder neck to the distal edge of the vermontanum by urethroscopy (Fig.1). A rough calculation was given by formula V1 or V2. V1 = pi abc/6 or V2 = 2/3 Sc. Calculated volumes of the prostate were compared with the weight of surgical specimens (TUR-P 27 cases, open surgery 7 cases). A good correlation was obtained by this method, i.e., regression equation V1: y = 1.21x + 9.68 (gamma = 0.9376); V2: y = 1.31x + 10.58 (gamma = 0.9471). This method is considered valuable for preoperative measurement of prostatic size, and is useful when evaluating changes in prostatic volume during non-surgical treatment.     

An immunohistochemical study of prostate antigen using an enzyme-labeled antibody technique

With an enzyme-labeled antibody technique, prostate antigen (PA) was studied immunohistochemically. PA was found to localize at epithelial cells and secretary materials in the lumen of prostatic tissue regardless of histological type. However, PA could not be detected in the interstitial area of the prostate. This technique may become useful for detection of local extension or distant metastasis of prostate cancer. An immunoelectronmicroscopical study of PA is now underway.     

The significance of serum prostate-specific antigen, gamma-seminoprotein and prostatic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hyperplasia (BPH), chronic prostatitis and acute prostatitis. PA has proved to be diagnostically more sensitive than PAP and gamma-Sm for the detection of prostatic cancer. Although PA may be elevated more frequently than PAP and gamma-Sm in patients with BPH, there are possibilities that these patients with elevated PA and normal PAP and gamma-Sm may have prostatic cancer or precancerous conditions not detectable in our routine diagnostic procedures. We report two cases of prostatic cancer with persistently elevated PA and diagnosed after repeated biopsies. Our data suggest that PA is a sensitive and useful tumor marker for the diagnosis of prostatic cancer. PAP and gamma-Sm in combination with PA may serve as more useful for differential diagnosis and confirmation of prostatic cancer.     

Cryotherapy

Since 1969 cryosurgical perineal destruction of the prostate has been developed at the University of Iowa for treatment of patients with prostatic cancer. The technique of this procedure has been the subject of previous reviews. This is a summary of our experience of patient survival and the effect on local prostatic cancer growth in those patients with various stages of the disease subjected to perineal cryosurgical destruction of their cancer. We also report briefly on our experience in the laboratory where the Dunning tumor model is used to study the effect of cryosurgery as well as combinations of immunological modifications.     

Immunoperoxidase staining of acid phosphatase in human prostatic tissue

The introduction of immunoperoxidase and the indirect immunoperoxidase technique made important contributions in histopathologic diagnosis of prostatic cancer. This staining can be performed on formalin-fixed paraffin-embedded tissue which is usually available. We have used this histopathologic staining technique in 56 patients. The tissues include primary and metastatic prostatic cancer tissue in addition to normal renal pelvis and bladder tissue from other patients. Our data indicate that acid phosphatase can be localized in prostatic cells but not in transitional cells. Therefore, immunohistochemical staining of prostatic acid phosphatase seems most useful to identify metastatic prostate adenocarcinoma or primary tumor and to differentiate them from intraductal prostatic transitional carcinoma or other transitional cell carcinomas.     

Three-dimensional display of the prostate based on transrectal ultrasonogram]

A software for a lap top computer to display prostatic contour three-dimensionally based on transrectal ultrasonograms was developed, and its clinical usefulness was examined. The prostatic contour of a case with prostatic cancer showed a typical irregular surface, and that of a case with prostatic hypertrophy had a smooth spherical shape, while that of a normal case had a flat shape. Each showed its characteristic shape. Estimation of the prostatic weight by assuming that the prostatic contour has ellipsoidal contour is a simple method for prostatic weight measurement, but it has a tendency to underestimate the weights, especially in normal cases. Three-dimensional display of the contour of prostatic cancer, prostatic hypertrophy, and normal prostate revealed that it could be estimated as ellipsoid in prostatic cancer or hypertrophy, while the normal prostatic contour was too flat to be calculated as such. Among 52 patients with benign prostatic hypertrophy who underwent transrectal ultrasonotomography before and during the anti-androgen therapy more than three time, nine cases showed transient reduction of more than 30% in prostatic weight and then reenlargement of more than 30%. In these cases, three-dimensional display of prostatic contour was done. The display was useful to visualize clearly which part reenlarged. Therefore, usefulness of the three-dimensional display of the prostate was verified.     

Clinical study on prostatic cancer detected incidentally by transurethral resection of the prostate

Transurethral resection of the prostate (TUR-P) was performed on 463 consecutive patients with clinically diagnosed benign prostatic hyperplasia (BPH) between April 1994 and June 2000. Pathological examinations of resected prostatic tissues revealed prostatic cancer in 15 (3.2%) of them. Eight (53.3%) of them were in stage A1, and 7 (46.7%) in stage A2. Between 15 cases with prostatic cancer and those with BPH, clinical features including age, serum prostate specific antigen (PSA) levels, prostatic volume, PSA density (PSAD), and resected prostatic tissue weight were compared. As a result, age was the only parameter related with prostatic cancer with a statistically significant difference. The higher the age, prostate cancer was found more frequently. Postoperatively, radical prostatectomy and antiandrogen therapy were performed in 1 and 9 cases, respectively. The remaining 5 cases are being followed with no treatment for prostatic cancer, and have shown no findings suggesting recurrence. These 15 cases are all living disease-free at present. It seems of importance to explain preoperatively the possible detection of prostatic cancer in association with TUR-P, particularly for elderly patients aged 80 years or older.     

The role of repeat transurethral resection in stage A1 carcinoma of the prostate

Between 1983 and 1987 repeat transurethral resection (TUR) was performed in 20 patients with a diagnosis of stage A1 prostatic carcinoma. The average weight of the resected tissue in the repeat TUR was 8.81 g (range 3-20 g). In 5 of 20 cases (25%) residual prostatic cancer was identified. By adding the number of foci with cancer obtained at the initial operation with the repeat TUR, 16 cases (80%) remained as A1 and 4 cases (20%) were reclassified (upstaged) to A2. The usefulness of this technique in the restaging of patients with incidental carcinoma of the prostate is analyzed.     

Cytokine profiling of prostatic fluid from cancerous prostate glands identifies cytokines associated with extent of tumor and inflammation

BACKGROUND: Cytokines are key mediators of inflammation that may relate to prostate cancer initiation and progression, and that may be useful markers of prostatic neoplasia and related inflammation. In order to better understand the relationship between cytokines and prostate cancer, we profiled cytokines in prostatic fluids obtained from cancerous prostate glands and correlated them to both cancer status and inflammatory grade. METHODS: Prostatic fluid was collected from fresh radical prostatectomy specimens and analyzed by cytokine antibody microarray. For comparison, cases were selected from patients with either minimal or extensive cancer volume on final pathology. Among the cytokines with the greatest difference between the tumor volume groups, eight had their levels quantitated by ELISA. In addition, the grade of prostatic inflammation by neutrophils, macrophages and lymphocytes was scored for each case and examined for correlations with cytokine levels. RESULTS: Among 174 cytokines analyzed, HGF was the most increased (6.57-fold), and along with IL18Bpa was significantly elevated in patients with extensive disease compared to those with minimal disease. IL17, GITR, and ICAM-1 were elevated in specimens with significant neutrophilic inflammation into gland lumina, and IL18Bpa, IL17, GITR, and ICAM-1 were elevated in specimens with significant lymphocytic inflammation in prostatic stroma. CONCLUSIONS: Prostatic fluid cytokines were identified that may be useful for early cancer detection and prognostication efforts and for assessment of prostatic inflammation, particularly if they can be found not only in prostatic fluids obtained ex vivo, but in expressed prostatic secretions or urine samples from men with prostates still in situ.     

Predictive value of prostatic adenocarcinoma after a negative prostate biopsy

OBJECTIVE: To investigate the predictive value (PV) for all prostate cancers and for clinically significant cancer undiagnosed after a 10-core biopsy protocol, as the 10-core transrectal ultrasonography-guided biopsy is considered the standard technique of prostatic biopsy due to its high rate of detection of prostatic adenocarcinoma. PATIENTS AND METHODS: In all, 132 consecutive radical prostatectomy (RP) specimens, with their corresponding 10-core biopsies, were reviewed. Cases with unilateral core involvement by prostate cancer were retained for study. Morphometric analysis was conducted on the biopsy-negative hemi-prostates to determine the PV of the biopsy protocol with respect to the size, position and clinical significance of the lesion. RESULTS: In all, 70 resected prostates (RP) had unilateral core involvement by prostate cancer. In 38 cases, there was cancer in the biopsy-negative hemi-prostates (group 1); in the remaining 32 the hemi-prostates were free of cancer (group 2). Group 1 was categorized by morphometric criteria. Specifically, 23 cases had one to eight foci of prostate cancer in the posterior nontransitional zone (NTZ) (group 1a), while 15 had two to six foci of prostate cancer in the transitional zone (TZ), or the anterior horn (AH) of the peripheral zone or the TZ and AH (group 1b). There were two cases with clinically significant prostate cancer in group 1a, and six in group 1b. CONCLUSIONS: The PV of a negative five-core biopsy protocol on a hemi-prostate is 54% for prostate cancer and 11% for clinically significant prostate cancer. Most clinically significant prostate cancers were in the AH/TZ of the prostate.     

Immunohistochemistry of prostatic acid phosphatase

The human prostatic acid phosphatase is a specific marker for the prostatic epithelial cells. By using an immunoperoxidase staining method for this enzyme, it is possible both to identify the prostatic epithelial cells and to recognize the prostatic origin of metastatic lesions of prostate cancer. Of the tissues containing prostatic epithelial cells from 120 patients, positive staining reaction was detected in 114 (95%), and negative in 6. In nonprostatic tissues from 242 patients, weak but positive staining reaction was detected in 8 (3.3%), including tissues from one renal cell carcinoma and 7 breast carcinomas. Of 27 patients in whom tumor tissues were tested at a time when tumor origin was unknown, the staining reaction was positive in 14 patients later found to have prostate cancer. It was negative in 6 patients with nonprostatic carcinoma and 7 patients with carcinoma of unknown primary. Although this immunohistochemical technique for prostatic acid phosphatase appears promising in diagnosing metastatic prostate cancer, its clinical significance and limitations remain unclear, and there are considerable technical problems yet to be solved. These problems are best approached by joint collaborative efforts of the various investigators interested in prostate cancer.