Cytological diagnosis of nodular hyperplasia and cancer of the prostate

The results of histological and cytologic examination of the material obtained from 289 transrectal punction biopsies of the prostate carried out in 278 patients were compared. Smears were prepared from bioptates and stained haematoxylineosin after the method of Papenheim, Papanicolaou modified by A. V. Rudenko and L. K. Koonitsa. They were also treated with acridin orange (1:10,000). The histological examination established cancer in 66, nodose hyperplasia--97, chronic prostatitis--38, tuberculosis--4, fibrosis of prostatic stroma--9 and unaltered tissue in 48 cases. Cancer was suspected in 8 cases, while prostatic tissue was not identified in preparations in 8 cases. The cytological study detected cancer in 73 and chronic prostatitis in 42 cases. Cancer was suspected in 8 cases. No tumor or epithelial elements were identified in 148 and 7 cases, respectively. The cytological diagnosis was valid in 81% and cancer was erroneously diagnosed in 18 cases. Malignancy was not detected in 11 cancer patients. The cytological analysis failed to identify any difference between nodose hyperplasia and unaltered tissue of the prostate. It proved to be able to verify clear- and dark-celled adenocarcinoma as well as small cell and polymorphocellular carcinoma. However, it also failed to identify cribriform carcinoma and anaplastic adenocarcinoma.     

Lactate dehydrogenase isoenzyme patterns of prostatic cancer and hyperplasia

Electrophoresis using agarose and lactic acid dehydrogenase (LDH) film plus scanning fluorometry provide a simple, fast method for precise and accurate measurement of serum and tissue LDH isoenzymes. Via this method prostate tissue LDH isoenzy mes were determined for over 200 patients with either hyperplasia or cancer. Increased LDH isoenzyme V activities generally selected out the cancer patterns, whereas peak isoenzyme I values did not distinguish between the two groups as well. The LDH index (I/V) only confirmed the LDH V values. That the metabolic changes of neoplasia precede histologic changes is suggested by two patients in whom repeat biopsies demonstrated cancer following elevated isoenzyme V levels in tissue originally considered benign.     

Benign prostatic hyperplasia and subsequent risk of bladder cancer

We evaluated the risk of bladder cancer in a cohort of 79,280 Swedish men hospitalised for benign prostatic hyperplasia (BPH), identified in the Swedish Inpatient Register between 1964 and 1983 and followed until 1989 via multiple record linkages with nationwide data on cancer registry, death and emigration. Standardised incidence ratios (SIRs), the ratios of the observed to the expected numbers of incident bladder cancers, were used to calculate the risk associated with BPH. The expected number was calculated by multiplying the number of person-years by the age-specific cancer incidence rates in Sweden for each 5-year age group and calendar year of observation. Analyses were stratified by BPH treatment, latency, calendar year and presence of genitourinary (GU) comorbid conditions. After excluding the first 3 years of follow-up after the index hospitalisation, we observed 506 incident bladder cancer cases during follow-up in the cohort. No overall increased risk of bladder cancer was apparent in our main analysis involving the entire BPH cohort. However, among BPH patients with transurethral resection of the prostate (TURP), there was an increased risk in all follow-up periods; SIRs of bladder cancer during years 4-6 of follow-up was 1.22 (95% confidence interval=1.02-1.46), 1.32 for 7-9 years of follow-up, and 1.47 for 10-26 years of follow-up. SIRs of bladder cancer among TURP-treated BPH patients were particularly elevated among those with comorbid conditions of the GU tract (e.g., stone, infection, etc.); 1.72, 1.74 and 2.01 for 4-6, 7-9, 10-26 years of follow-up, respectively, and also for those whose diagnoses occurred before 1975, when TURP was more likely to be performed by a urologist than a general practitioner: 1.87, 1.90 and 1.74, respectively. These findings suggest that BPH overall is not associated with bladder cancer risk. However, among men treated with TURP, particularly those with other comorbid GU tract conditions, risk of bladder cancer was elevated.     

Leptin in relation to prostate cancer and benign prostatic hyperplasia

The aim of our study was to determine whether leptin, a hormone implicated in both energy-balance and reproductive function, is involved in the etiology of prostate cancer or benign prostatic hyperplasia (BPH). We compared the serum leptin levels of 43 cases of incident prostate cancer, 41 patients with BPH, and 48 healthy controls, all recruited in Athens, Greece. Multiple logistic regression modeling was used, with adjustment for age, height, body mass index, education, estradiol, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin and insulin like growth factor 1. Odds ratios per 4 ng/ml increment of leptin were 0.70 [95% confidence interval (CI) (0.32,1.55)] for prostate cancer and 1.06 [95% CI (0.67,1.67)] for BPH. After adjustment for body mass index, serum leptin levels were not significantly correlated with levels of any of the other hormones under study. Leptin levels are unlikely to affect the risk of either prostate cancer or BPH substantially. Int. J. Cancer 76:25–28, 1998.© 1998 Wiley-Liss, Inc.     

Family history of cancer and the risk of prostate cancer and benign prostatic hyperplasia

We analysed the relation between family history of cancer in first-degree relatives and risk of prostate cancer (PC) and benign prostatic hyperplasia (BPH) using data from a multicentric case-control study conducted in Italy from 1991 to 2002 on 1,294 cases of incident, histologically confirmed PC, 1,369 cases of BPH and 1,451 men admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (OR) of PC and BPH, adjusted for age and other confounders. Men with a family history of PC had an OR of PC of 4.0 (95% confidence interval [CI] 2.5-6.5), and the risk was higher when the proband was younger, when 2 or more relatives were affected or when the affected relative was a brother. The risk of PC was also increased in men with a family history of cancer of the ovary (OR = 6.2, 95% CI 1.2-32), bladder (OR = 3.5, 95% CI 1.6-7.4) and kidney (OR = 3.1, 95% CI 1.1-8.5). An involvement of breast/ovarian cancer predisposition genes in a small proportion of PCs was suggested by the cluster of these cancers in female relatives of a few PC cases. The risk of BPH was increased in men with a family history of bladder cancer (OR = 2.2, 95% CI 1.0-5.0) but not PC (OR = 1.2, 95% CI 0.7-2.2). Our study adds further information on the association of family history of cancer and risk of PC and is, to our knowledge, the first comprehensive epidemiologic information on family history of cancer and risk of BPH.     

Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level

BACKGROUND: The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (> or =60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately.     

前列腺癌与增生组织雄激素受体基因微卫星多态性的研究

目的探讨雄激素受体基因CAG微卫星多态性与前列腺癌以及前列腺增生的关系.方法运用聚合酶链反应-单链构象多态性分析法(PCR-SSCP),对18例良性前列腺增生、37例前列腺腺癌组织进行雄激素受体基因CAG微卫星数量测定.结果良性前列腺增生、B期、C～D期前列腺癌、高分化、中分化以及低分化前列腺癌的雄激素受体基因CAG均数分别是26.11±3.35、25.04±1.88、22.14±2.64、25.6±1.36、24.29±3.19和23.64±2.64.其均数比较,良性前列腺增生与C～D期前列腺癌以及低分化前列腺癌间差异有显著性(P=0.001～0.016),良性前列腺增生与B期前列腺癌、中分化及高分化前列腺癌其差异无显著性(P=0.249～0.636).结论雄激素受体基因CAG微卫星数量的差异性可能与良性前列腺增生以及不同类型前列腺癌的发病机制相关.     

前列腺癌和前列腺增生组织Hepsin表达及其临床意义

目的:探讨Hepsin在前列腺癌组织中的表达,并分析其与前列腺癌临床分期及病理分级之间的关系.方法:免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结(SP)法检测68例前列腺癌、40例前列腺增生组织中Hepsin蛋白的表达,并分析其与临床分期、病理分级之间的关系.结果:Hepsin蛋白在前列腺癌组织和前列腺增生组织中阳性表达率分别为86.76% (59/68)和45.00%(18/40),差异有统计学意义,χ2=21.47,P<0.001;其阳性率在前列腺癌不同临床分期中差异有统计学意义(χ2=9.07,P=0.004),而在Gleason评分高与低分组之间差异无统计学意义,χ2=1.15,P=0.476.结论:Hepsin可作为前列腺癌的一个诊断指标,其与前列腺癌临床分期密切相关,有可能在前列腺癌的发生发展中起重要作用.     

Beta-glucuronidase activity in prostatic carcinoma and benign prostatic hyperplasia

Beta-glucuronidase activity was extracted from prostatic carcinomas and hyperplastic prostates. It was 3.6-fold higher (P less than 0.0001) in prostatic carcinoma than in prostatic hyperplasia. Analysis for isoenzymes of prostatic beta-glucuronidase by disc-gel electrophoresis in nondenaturing polyacrylamide gels demonstrated only one form of the enzyme. Histochemically, enzymatic activity was observed almost entirely in epithelial cells in both prostatic carcinoma and benign prostatic hyperplasia.     

Catechol-O-methyltransferase gene polymorphisms in benign prostatic hyperplasia and sporadic prostate cancer.

Various carcinogenic metabolites, including catechol estrogens, play a role in malignant transformation. An enzyme that is capable of neutralizing the genotoxic effects of these compounds is catechol-O-methyltransferase (COMT). A variant form of this enzyme has been shown to reduce its activity by up to 4-fold; thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. To test this hypothesis, the genetic distribution of three different COMT polymorphisms at codon 62 (C-->T), codon 72 (G-->T), and codon 158 (G-->A) were analyzed in 131 normal healthy subjects, 134 BPH, and 178 sporadic prostate cancer samples from a Japanese population. Results of these experiments show that the variant genotype at codon 62 (P = 0.060) and codon 158 (P = 0.047) are risk factors for prostate cancer but not BPH when compared with normal controls. Odds ratio (OR) and 95% confidence interval (95% CI) for cancer were 3.24 and 1.38 to 7.61, respectively, for codon 62 T/T genotype when compared with wild type. At codon 158, the A/A variant for cancer had an OR of 3.00 with a 95% CI of 1.38 to 6.54 compared with wild type. Codons 62 and 158 were in linkage disequilibrium (LD), and when compared with the C-G haplotype, other types (C-A, T-G, T-A) were observed to be associated with prostate cancer (P = 0.040) but not BPH. Codon 72 on the other hand, was not in LD with either codon 62 or 158. The homozygous variant on codon 72 was rare in this Japanese population, and the heterozygous G/T at this codon was not associated with either prostate cancer or BPH. When evaluating the risk of COMT polymorphisms with stage or grade of cancer, no associations were observed for any of the genotypes with the exception of a tendency (P = 0.096) for the variant A allele on codon 158 to be correlated with higher stages (> or = T3) of cancer. This is the first report that shows the polymorphisms of COMT to be associated with sporadic prostatic carcinogenesis. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of prostate cancer.     

5'-nucleotidase activity in prostatic carcinoma and benign prostatic hyperplasia

In light of previous reports of alterations in 5'-nucleotidase activity in neoplastic conditions, 5'-nucleotidase activity was examined histochemically in tissue sections and quantified biochemically in extracts of human hyperplastic prostates and prostatic carcinomas obtained surgically. The 5'-nucleotidase activities per mg protein in extracts of 29 prostatic carcinomas were lower (P less than 0.0005) than in extracts from 10 samples of benign prostatic hyperplasia. The 5'-nucleotidase activity per mg protein in extracts of prostatic carcinoma from the 29 patients correlated (R = -0.369, P = 0.049) with the degree of histological differentiation; the extracts of poorly differentiated carcinomas contained low levels of 5'-nucleotidase. When age and histological differentiation (Gleason's grade) were adjusted, the enzyme activity per mg protein correlated (R = 0.242, P = 0.004) with patient survival. When all three parameters were considered together, i.e., histological grade of the tumor, 5'-nucleotidase extracted from the tumor, and age of the patient, they were found to be mutually complementary for the prediction of patient survival (R = 0.388, P = 0.0001). To our knowledge, this is the first report that prostatic epithelium expresses 5'-nucleotidase; further work will be required to define the reasons for the high levels of activity observed in prostates without cancer and for the decrease in the activity in prostatic carcinoma.     

Arginase activity in prostatic tissue of patients with benign prostatic hyperplasia and prostatic carcinoma

We studied arginase activity in human prostatic tissue in 15 patients with benign hyperplasia and 27 patients with prostatic carcinoma. Arginase specific activity is greater (p less than 0.0001) in prostatic carcinomas than in hyperplastic prostates. Arginase specific activity is correlated inversely (p less than 0.0001) with the histological grade of the tumor.     

Errors, hazards and complications in transurethral resection of prostatic hyperplasia

Transurethral resection of hyperplastic prostate was carried out in 667 patients. Complications associated with the intervention occurred in 146 (21.89%) patients: intraoperative in 31 (4.6%), immediately after surgery in 68 (10.2%), and during remote period in 47 (7.04%) patients. Causes of complications are discussed, probable errors in transurethral resection are enumerated, and recommendations on prevention of complications in endosurgery for prostatic hyperplasia are offered.     

Abnormal DNA ploidy and proliferative patterns in superficial colonic epithelium adjacent to colorectal cancer

Superficial colonic cells were taken from normal-appearing mucosa at 2, 5, and 10 cm proximal and distal to colorectal cancer margins in 37 patients. The DNA ploidy and proliferative pattern of each sample were determined using flow cytometry. In 11 patients, histology of mucosal sections from the same sites also was analyzed. We found a higher frequency of aneuploidy than previously reported in mucosa up to 10 cm from a colorectal cancer; 62% (23/37) of the primary cancers were aneuploid, and of these, 48% (11/23) were associated with adjacent aneuploid mucosa. The mucosa adjacent to the 14 diploid cancers had only diploid characteristics. The proliferative activity (as reflected by synthetic (S) phase fraction) of aneuploid cancers (21.1 +/- 2.0% SEM) and aneuploid mucosa as far as 10 cm away (21.2 +/- 2.1% SEM) was higher than in normal controls (10.2 +/- 0.7% SEM) (P less than 0.0005). Parallel cytology excluded shed cancer cells as an explanation for these findings. Histology showed diffuse, generally mild and reactive, mucosal abnormalities in eight of 11 patients. Ploidy did not correlate with histologic abnormalities. The findings of aneuploidy and high S-phase fraction in uninvolved superficial mucosa provide evidence for a field defect in mucosa adjacent to colorectal cancer and support the concept that the large bowel mucosa behaves as a unit in carcinogenesis.     

常规超声及超声造影对结节性肝癌及肝局灶性结节性增生的鉴别诊断价值

目的 分析结节性肝癌及肝局灶性结节性增生(FNH)的超声特征及超声造影特征.方法 回顾性分析40例结节性肝癌患者(结节性肝癌组)及40例FNH患者(FNH组)的临床资料,所有患者均接受常规超声及超声造影检查,观察两组患者的超声特征及不同时相的超声造影特征.结果 结节性肝癌组患者门静脉癌栓(22.5％vs 0)、肝硬化(60.0％vs 15.0％)及淋巴结肿大(20.0％vs 2.5％)的发生率高于FNH组,中心瘢痕(15.0％vs 62.5％)的发生率低于FNH组,病灶位于肝包膜下的比例(22.5％vs 52.5％)低于FNH组,差异均有统计学意义(P﹤0.05).两组患者的超声动脉相均以高增强为主,动脉相增强模式比较,差异无统计学意义(P﹥0.05);对于门脉相及延迟相,结节性肝癌组患者均以低增强为主,FNH组患者均以等低增强为主,两组患者的门脉相及延迟相增强模式比较,差异均有统计学意义(Z=2.754、3.556,P﹤0.01).结节性肝癌组患者的上升时间(RT)[(21.9±8.7)s vs(27.8±9.2)s]、达峰时间(TTP)[(29.6±9.3)s vs(36.1±11.8)s]及平均通过时间(mTT)[(102.1±37.7)s vs(136.2±42.1)s]均明显短于FNH组,灌注指数(PI)[(122.8±31.6)vs(85.9±22.2)]明显高于FNH组,差异均有统计学意义(P﹤0.01).结论 结节性肝癌和FNH具有较为典型的超声特征及超声造影特征,可对两者进行较准确的鉴别诊断.     

Metabolic markers in blood can separate prostate cancer from benign prostatic hyperplasia

Background:

An individualised risk-stratified screening for prostate cancer (PCa) would select the patients who will benefit from further investigations as well as therapy. Current detection methods suffer from low sensitivity and specificity, especially for separating PCa from benign prostatic conditions. We have investigated the use of metabolomics analyses of blood samples for separating PCa patients and controls with benign prostatic hyperplasia (BPH).

Methods:

Blood plasma and serum samples from 29 PCa patient and 21 controls with BPH were analysed by metabolomics analysis using magnetic resonance spectroscopy, mass spectrometry and gas chromatography. Differences in blood metabolic patterns were examined by multivariate and univariate statistics.

Results:

By combining results from different methodological platforms, PCa patients and controls were separated with a sensitivity and specificity of 81.5% and 75.2%, respectively.

Conclusions:

The combined analysis of serum and plasma samples by different metabolomics measurement techniques gave successful discrimination of PCa and controls, and provided metabolic markers and insight into the processes characteristic of PCa. Our results suggest changes in fatty acid (acylcarnitines), choline (glycerophospholipids) and amino acid metabolism (arginine) as markers for PCa compared with BPH.     

Gene expression profile in the peripheral blood of patients with prostate cancer and benign prostatic hyperplasia

Background: Prostate cancer consists of multifactorial and multifocal events, generating differential gene expression in tumor cells. Methods: The molecular profile of 14 gene expression was analyzed through cDNA array in blood samples of patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Results: Messenger RNA from patient's blood showed significant differences between PCa and BPH groups only for the NOS3 gene, with an occurrence chance for PCa 5.8-fold higher than BPH disease. Conclusion: The NOS3 gene expression in the patient's blood may be used as a putative biomarker for prostate cancer.