Vimentin and cytokeratin expression in nodular hyperplasia and carcinoma of the prostate.

AIM--To assess the value of vimentin and cytokeratin (CK) intermediate filament proteins (IFPs) in distinguishing between nodular hyperplasia and carcinoma of the prostate and in predicting prognosis in prostatic cancer. METHODS--Fifteen carcinomas and 49 cases of nodular hyperplasia were studied using frozen sections and monoclonal antibodies to CK and vimentin IFPs. RESULTS--There was no statistically significant difference in vimentin expression between nodular hyperplasia and carcinoma. The luminal epithelium in both also reacted with antibodies which detect CK8, 18 and 19. CK 7 expression was found in 57% of cases of nodular hyperplasia and was not identified in any carcinoma. There was a reaction with antibodies to CK1, 2, 3, 4, 10, 11, and 13 in only a minority of cases. There was no statistically significant difference in vimentin and CK reactivity in high and low grade carcinomas. CONCLUSION--Neither vimentin nor CK expression assists in establishing whether a prostatic lesion is benign or malignant or in predicting the biological behaviour of a prostatic carcinoma.     

Complexed and total PSA in patients with benign prostatic hyperplasia and prostate cancer

This study compares the diagnostic utility of complexed prostate-specific antigen (cPSA), total PSA (tPSA) and their ratios with free PSA (fPSA) for benign prostatic hyperplasia (BPH) and prostate cancer. This is though to be the first study to evaluate cPSA in the ethnic population of Saudi Arabia. Serum samples were collected from 54 patients (aged over 50) and assayed for tPSA, cPSA and fPSA. Thirty-five patients were histologically and clinically proven to have BPH and 19 patients were proven to have cancer. Sensitivity, specificity and ROC curves were calculated. With a cPSA cut-off of 4 ng/mL the sensitivity was 79%, the specificity was 34%, and the positive and negative predictive values (PPV and NPV) were 39% and 75%, respectively. At the same cut-off for tPSA, the sensitivity was 84%, the specificity was 29%, and the PPV and NPV were 39 and 77%, respectively. The sensitivity for both tests was lower at a cut-off of 20 ng/mL but the specificity increased to 77% for cPSA and 69% for tPSA. The areas under the receiver operating characteristic (ROC) curves were found to be 0.608 for tPSA and 0.559 for cPSA (P = 0.69). The incidence of prostate cancer in the Saudi population may be lower than that in Western populations. The data presented show little advantage in using cPSA over tPSA for discriminating BPH and prostate cancer in the population studied.     

Hepatocellular carcinoma associated with focal nodular hyperplasia

We describe a hepatocellular carcinoma partially surrounded by focal nodular hyperplasia in a 65-year-old female patient. In order to clarify the relationship of the hepatocellular carcinoma and the adjacent focal nodular hyperplasia, clonal analysis was conducted. The clonal analysis was based on the methylation pattern of the polymorphic X-chromosome-linked androgen receptor gene (HUMARA). The allelic bands from the amplification of the focal nodular hyperplasia and of the hepatocellular carcinoma showed a significant reduction in the intensity of one of the two alleles as compared with two alleles of equal intensity in the buff coat after HhaI digestion, which indicated that these two parts were monoclonal. However, the inactivated allele in the focal nodular hyperplasia and that in the hepatocellular carcinoma were not identical. Therefore, the focal nodular hyperplasia and hepatocellular carcinoma probably derived from the clonal expansion of two different clones.     

血清PSA与PAP检测在前列腺癌诊断中的应用价值

目的：探讨血清前列腺特异性抗原（PSA）及酸性磷酸酶（PAP）对前列腺癌患者的辅助诊断价值。方法：采用免疫放射分析法（IRMA）对98例前列腺癌患者,45例前列腺良性疾患及40例正常健康人进行血清PSA,PAP测定。结果：前列腺癌组PSA,PAP水平均显著高于前列腺良性疾患组及正常对照组（P＜0．01）,PSA对前列腺癌的灵敏性为93．9％）,特异性为93．3％,PAP对前列腺癌的灵敏性为71．％,特异性为91．1％。结论：血清PSA与PAP检测对前列腺癌的早期诊断有较高的临床价值,是临床分期, 效监测及判断预后的重要参考指标。     

The significance of PSA/IGF-1 ratio in differentiating benign prostate hyperplasia from prostate cancer

The importance of insulin-like growth factor 1 (IGF-1) in human serum for the early diagnosis of prostate cancer is controversial. The IGF-1/PSA ratio may improve the performance of prostate specific antigen (PSA) as a prostate cancer marker. IGF-1, along with PSA and free PSA concentration, was measured in the serum of 34 patients with prostate cancer and in 131 patients with benign prostatic hyperplasia (BPH). Although IGF-1 concentration did not significantly differ between the groups, PSA/IGF-1 ratio could clearly distinguish the two groups. In patients with cancer but not in patients with BPH, IGF-1 concentration correlated with PSA and free PSA. The values of PSA and free PSA correlated with each other for both groups. Receivers Operating Curve (ROC) analysis indicated a better sensitivity to specificity ratio for PSA/IGF-1 than for PSA or Free/Total (F/T) PSA.     

Serum and tissue measurements of CA72-4 in patients with endometrial carcinoma.

AIMS: To evaluate the clinical usefulness of CA72-4 as a serum tumour marker for endometrial carcinoma and to investigate its immunohistochemical localisation in endometrial carcinoma cells. METHODS: Serum concentrations of CA72-4 were determined in 72 patients with endometrial carcinoma. Immunohistochemical localisation of CA72-4 was investigated using the streptavidin-biotin method, using monoclonal antibodies B72.3 and CC49. RESULTS: Serum CA72-4 was increased above the cut off value in 31.9% of the patients with endometrial carcinoma. Serum CA72-4 positivity was correlated with depth of myometrial invasion, adnexal metastasis, lymphovascular space involvement, and pelvic and para-aortic lymph node metastasis. Multivariate analysis showed a significant correlation between serum CA72-4 positivity and adnexal metastasis. The serum concentrations of CA125 and CA19-9, which could be tumour markers for endometrial carcinoma, were measured at the same time. In seven of 72 patients increased concentrations of serum CA72-4 were found while those for CA125 and CA19-9 were within the normal ranges; in four of the seven patients the disease had spread beyond the uterus. Immunohistochemical positivity for CA72-4 antigen was 76.9% and occurred in the tumour cell membrane and cytoplasm. There was no significant difference in immunohistochemical positivity between patients with increased CA72-4 and those with normal CA72-4 values. CONCLUSIONS: The measurement of serum concentrations of CA 72-4 could be useful for predicting and monitoring the progress of disease-for example, extracorporeal spread.     

Hepatocellular carcinoma, adenoma, and focal nodular hyperplasia. Comparative histopathologic study with immunohistochemical parameters

For the evaluation of differential diagnostic parameters, hepatocellular carcinoma (HCC, n = 26), liver cell adenoma (n = 4), focal nodular hyperplasia (n = 8), and secondary liver tumors (n = 15) were studied with histologic and immunohistochemical methods. The study was performed on formalin-fixed, paraffin-embedded tissue sections, and, in some cases, also on frozen sections. The diagnostic contribution of the demonstration of alpha-fetoprotein, alpha-antitrypsin, hepatitis B surface antigen, carcinoembryonic antigen (CEA), and biliary glycoprotein I (BGPI), compared with routine hematoxylin-eosin and reticulin stains was evaluated. For the differentiation between HCC, adenoma, and focal nodular hyperplasia, immunohistochemistry contributed less than the strict application of histologic criteria. Immunohistochemistry of CEA and BGPI, however, appeared to be of help in differentiating between primary and secondary liver tumors as follows: CEA is consistently absent in liver cell tumors, while a bile canalicular staining pattern was seen in 80% of HCC due to the presence of BGPI reactivity.     

Concomitant hepatocellular carcinoma and non-Hodgkin's lymphoma in a patient with nodular regenerative hyperplasia

Hepatocellular carcinoma (HCC) is the most common primary cancer in the liver. Liver invasion of non-Hodgkin's lymphoma (NHL) is also often observed. But simultaneous existence of HCC and NHL in a liver is extremely rare. Such patients reported previously had cirrhotic livers. Herein is reported a patient who simultaneously had HCC and NHL in a liver without cirrhosis, but with nodular regenerative hyperplasia (NRH). NHL was of the diffuse large B-cell type. Lymphoma cells invaded the portal vein, and formed thrombi. These thrombi would contribute to the development of NRH by decreasing portal vein blood flow. HCC was of the well-differentiated type and there was a 2 cm-sized nodule at the lateral segment. There is the possibility that NRH was associated with the HCC because NRH is reported as a premalignant lesion. HCC and NHL were colocalized in the liver without hepatic virus infection or cirrhosis, although common cause(s) of development of these malignancies remain unclear in the present case.     

Focal nodular hyperplasia with calcification and ossification

We describe a 33-year-old woman with Crohn's disease, who presented with recurrent episodes of small bowel obstruction. A solitary liver lesion was discovered incidentally by abdominal ultrasound. Pathological examination of the resected specimen revealed features typical of focal nodular hyperplasia together with uncommon findings including calcification, ossification and fibrous obliteration of blood-filled "cysts", changes more commonly associated with regression in hepatic haemangiomas. This report strengthens the favoured hypothesis that a vascular malformation underlies the pathogenesis of focal nodular hyperplasia.     

Focal nodular hyperplasia with concomitant hepatocellular carcinoma: a case report and clonal analysis

This report describes a hepatocellular carcinoma (HCC) with concomitant focal nodular hyperplasia (FNH) in a 56 year old Chinese man. There were two well circumscribed tumours measuring 3 x 2.5 x 2 cm and 2 x 1.5 x 1.5 cm. The larger mass was grey and soft with a small area of bleeding and necrosis and an intact capsule. The smaller mass was yellow and had no capsule. Clonal analysis was carried out to clarify the relation between the HCC and the adjacent FNH. The clonal analysis was based on the methylation pattern of the polymorphic X chromosome linked androgen receptor gene (HUMARA). In FNH, after HpaII digestion, the allelic bands showed two well defined peaks. The intensity of the two peaks in the DNA from cirrhotic tissue did not differ significantly, consistent with a random pattern of X chromosome inactivation. However, in HCC, after HpaII digestion, the allelic bands differed significantly in intensity. Therefore, there was a typical polyclonal pattern of inactivation in FNH but the HCC was interpreted as being monoclonal.     

PSA immunoreactivity in a parotid oncocytoma: A diagnostic pitfall in discriminating primary parotid neoplasms from metastatic prostate cancer

Prostate-specific antigen (PSA) is secreted by both normal and neoplastic acinar cells of the prostate gland, and the immunohistochemical detection of PSA is widely accepted as an excellent method for confirming the prostatic origin of metastatic tumor implants in men with prostate cancer. Less recognized is the observation that certain nonprostatic tissues and their neoplastic counterparts also secrete PSA. As one example, salivary gland ducts and certain salivary gland neoplasms have been reported to be immunoreactive for PSA. Potentially, this nonspecificity could be a diagnostic pitfall when using immunoperoxidase on fine-needle aspiration (FNA) biopsy specimens to differentiate metastatic prostate cancer from primary salivary gland tumors. We report on a case where strong PSA immunoreactivity of a parotid oncocytoma led to its confusion with metastatic prostate cancer. Diagn. Cytopathol. 1998;19:221–225. © 1998 Wiley-Liss, Inc.     

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scarlike fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.     

Androgen receptor gene amplification increases tissue PSA protein expression in hormone-refractory prostate carcinoma.

Androgen receptor (AR) gene amplification was analysed by fluorescence in situ hybridization (FISH) from 24 paraffin-embedded prostate carcinoma samples recurring locally during hormonal therapy and prostate-specific antigen (PSA) expression from 15/24 of these samples was studied by immunohistochemistry (IHC). AR gene amplification was detected in 29 per cent (7/24) of the recurrent tumours. Using modified Histoscore (MHS), PSA immunostaining in the AR gene-amplified tumours (133+/-102) was twice as high (p=0.054) as in tumours with no amplification (66+/-79) and a statistically significant (p=0.026) association between AR gene amplification and PSA positivity was found when MHS>/=20 was considered positive for PSA. AR gene copy number was positively correlated with PSA MHS in the AR gene-amplified tumours (r=0.893, p=0.012). Histological grade, Gleason's score, and tumour stage did not differ significantly between patients with and without AR gene amplification. In conclusion, these results indicate that AR gene amplification leads to up-regulation of PSA gene (and possibly other androgen-dependent genes), and that patients with AR gene amplification may have elevated serum PSA concentrations without a clear correlation with actual tumour burden.     

Urinary microbiota in patients with prostate cancer and benign prostatic hyperplasia

Introduction

Inflammation is associated with promotion of the initiation of various malignancies, partly due to bacterial infection-induced microenvironmental changes. However, the exact association between microbiota in urine, seminal fluid and the expressed prostatic secretions and benign prostatic hypertrophy and prostate cancer is not clear.

Material and methods

In the present study, we investigated the type of microbiota in the expressed prostatic secretions (EPS) of patients with prostate cancer and benign prostatic hyperplasia (BPH) by the polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) method using universal bacterial primers. In order to understand the possible association between various bacteria and prostate cancer, quantitative real-time PCR assay was performed to quantify the amount of strains of bacteria in urine, EPS and seminal fluid.

Results

The prostate cancer group had a significantly increased number of Bacteroidetes bacteria, Alphaproteobacteria, Firmicutes bacteria, Lachnospiraceae, Propionicimonas, Sphingomonas, and Ochrobactrum, and a decrease in Eubacterium and Defluviicoccus compared to the BPH group. The number of Escherichia coli in the prostate cancer group was significantly decreased in urine and increased in the EPS and seminal fluid, while the number of Enterococcus was significantly increased in the seminal fluid with little change in urine and EPS.

Conclusions

Based on these results, we suggest that there are significant changes in the microbial population in EPS, urine and seminal fluid of subjects with prostate cancer and BPH, indicating a possible role for these bacteria in these two conditions.     

Differential expression of MSX2 in nodular hyperplasia, high-grade prostatic intraepithelial neoplasia and prostate adenocarcinoma

One of the common features in advanced prostate cancer is bone metastasis. In this study, we investigated the clinical relevance of a bone factor, MSX2, in predicting the metastatic ability of prostate adenocarcinoma. Evaluation of MSX2 expression was performed using prostate cell lines as well as patient specimens. A sharp decrease in MSX2 was found in primary prostate cancer cells, 22Rv1, when compared with the non-malignant counterparts, followed by a gradual increase in more aggressive prostate cancer cell lines. Interestingly, the MSX2 protein was upregulated and predominantly expressed in the nucleus in aggressive prostate cancer cell line, C4-2b, compared with the less aggressive 22Rv1. Consistent with the in vitro results, MSX2 nuclear expression was significantly higher in nodular hyperplasia when compared with high-grade prostatic intraepithelial neoplasia (PIN), while MSX2 nuclear expression in prostate adenocarcinoma was higher than that in high-grade PIN. Importantly, MSX2 expression was increased significantly in tumors with metastasis compared with those without metastasis. Finally, MSX2 nuclear scores were significantly increased in patients with preoperative serum PSA >20 ng/mL. No correlation between MSX2 nuclear score and Gleason score was found. Taken together, MSX2 may serve as a potential biomarker in predicting primary prostate tumors with higher metastatic capability.     

Fibrolamellar carcinoma of the liver: the malignant counterpart of focal nodular hyperplasia with oncocytic change

A case of fibrolamellar carcinoma (FLC) in a noncirrhotic liver of a 20-year-old man is described. Gross features and the presence, among the tumor cells, of bile ducts, of thick-walled blood vessels and nerves, and, ultrastructurally, of myofibroblast-like cells are the most significant findings, suggesting that FLC is the malignant counterpart of focal nodular hyperplasia with oncocytic change. Histochemical and immunohistochemical methods demonstrate the presence inside the oncocytic tumor cells of copper, copper-binding protein, and alpha 1 antitrypsin. The pathogenesis and the significance of these findings then are discussed and related to the restricted capacity of oncocytic cells to fulfill normal cellular function.     

PSA-PSMA profiles and their impact on sera PSA levels and angiogenic activity in hyperplasia and human prostate cancer

Aim

The relevance of prostate specific antigen (PSA)-prostate specific membrane antigen (PSMA) profiles in pathologic prostate (hyperplasia and cancer) has not been fully understood. The aim of this study is to investigate the impact of PSA-PSMA profiles on sera PSA levels and angiogenic activity in benign prostate hyperplasia (BPH) and prostate carcinoma (PC).

Patients and methods

The study has been carried out in 6 normal prostate (NP), 29 BPH and 33 PC with dominant Gleason grade > 8. Immunohistochemical analysis has been performed. Monoclonal antibodies 3E6 and ER-PR8 have been used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis has been made by CD34 immune marker. Serum levels of PSA have been assayed by Immulite autoanalyser.

Results

The study of each protein separately among sera PSA levels showed that PSMA expression and angiogenic activity have the highest intensity in PC patients with serum PSA levels > 20 ng/mL. Nevertheless, the lowest tissue PSA expression was found in PC patients with this latter sera PSA group. The most relevant results showed that in PC patients (PSA+, PSMA+) and (PSA–, PSMA+) profile were found to be inversely related to sera PSA levels. In PC patients, a high immunoexpression of (PSA+, PSMA+) profile has detected in the sera PSA group > 20 ng/mL; whereas a high immunoexpression of (PSA–, PSMA+) profile was detected in the sera PSA group between 0 and 4 ng/mL. The highest angiogenic activity was found in PC patients with (PSA+, PSMA+) profile.

Conclusions

Our findings clearly have supported the feasibility of PSA-PSMA profiles to improve in vivo diagnostic and therapeutic approaches in prostate cancer patients.