Role of screening in detection of clinically localized prostate cancer

The aim of this study was to confirm the role of screening by determining the percentage of clinically localized prostate cancer (stage A and B) in patients with prostate cancer detected on screening and in those presenting to urologic clinic for the symptoms of urination impairment or ostalgia. During the study, 1,000 men aged > or = 50 from the community of Cepin and village of Josipovac near Osijek were examined. The subjects with elevated concentration of total prostate specific antigen and/or digital rectal examination suspect of carcinoma underwent transperineal biopsy of the prostate. Clinical staging was performed in patients with prostate cancer detected on screening, and data on clinical staging for prostate cancer patients treated during the 1996-1997 period were retrieved from patient files of the Department of Urology, University Hospital "Osijek". On screening, 28 (80%) patients with localized prostate cancer and seven (20%) patients with metastases were detected. In the group of patients examined on an outpatient basis for the signs and symptoms of prostatism, there were 30 (83.4%) patients with metastases and only six (16.6%) patients with localized prostate cancer. Study results indicated that an early diagnosis of prostate cancer could be made by use of noninvasive and inexpensive methods that cause no major discomfort to the patient. Accordingly, these results appear to strongly support such screening in men, if not in all those aged over 50, then at least in the otherwise healthy, 50-70 age group.     

Comparison of digital rectal examination and prostate specific antigen in early detection of prostate cancer

This study compares the value of digital rectal examination (DRE) and prostate specific antigen (PSA) determination in the detection of prostate cancer. 1,000 men aged > or = 50 from the Osijek surroundings were examined. The subjects with prostatitis were excluded from the study. The subjects with elevated concentration of total prostate specific antigen and/or digital rectal examination suspect of carcinoma underwent prostate biopsy. The rate of prostate cancer detection showed to be 3.3% for PSA > 4 ng/ml, 2% for abnormal finding of DRE, and 3.7% for combination of the two methods. Out of 35 patients with prostate cancer detected, 19 had suspect DRE finding and 32 had PSA exceeding 4 ng/ml. Thus, PSA pointed to the diagnosis of prostate cancer in 91.4%, and abnormal finding of DRE in 54.2% of cases, the difference being statistically significant. The positive predictive value was 48.7% for abnormal finding of DRE, 47% for PSA > 4 ng/ml, and 80.0% for the combination of both. Although PSA determination detected a considerable proportion of tumors missed on DRE, the former alone was found to be insufficient as a screening method because of its inadequate sensitivity. When combined with digital rectal examination, the probability of prostate cancer detection increased considerably.     

Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer

Introduction

We previously identified prostate cancer (PCa)-associated aberrant glycosylation of PSA, where α2,3-linked sialylation is an additional terminal N-glycan on free PSA (S2,3PSA). We then developed a new assay system measuring S2,3PSA using a magnetic microbead-based immunoassay. We compared the diagnostic accuracy of conventional PSA and percent-free PSA (%fPSA) tests.

Methods

We used MagPlex beads to measure serum S2,3PSA levels using anti-human fPSA monoclonal antibody (8A6) for capture and anti-α2,3-linked sialic acid monoclonal antibody (HYB4) for detection. We determined the cutoff values in a training test and measured serum S2,3PSA levels in 314 patients who underwent biopsy, including 138 PCa and 176 non-PCa patients with PSA of <10.0 ng/ml. Serum S2,3PSA levels were presented as mean fluorescence intensity (MFI). Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of total PSA, %fPSA, and S2,3PSA.

Results

We determined an MFI cutoff value of 1130 with a sensitivity of 95.0% and specificity of 72.0% for the diagnosis of PCa in the training test. In the validation study, the area under the curve for the detection of PCa with S2,3PSA was 0.84, which was significantly higher than that with PSA or %fPSA.

Conclusions

Although the present study is small and preliminary, these results suggest that the measurement of serum S2,3PSA using a magnetic microbead-based immunoassay may improve the accuracy of early detection of PCa and reduce unnecessary prostate biopsy.     

Genome-wide detection of LOH in prostate cancer using human SNP microarray technology

Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In this study we assessed the potential of the Affymetrix GeneChip HuSNP mapping assay for detecting genome-wide LOH in prostate tumors. We analyzed two human prostate cell lines, P69SV40Tag (P69) and its tumorigenic subline, M12, and 11 prostate cancer cases. The M12 cells showed LOH in chromosomes 3p12.1-p22.1, 11q22.1-q24.2, 19p13.12, and 19q13.42. All of the prostate cases with informative single-nucleotide polymorphism (SNP) markers showed LOH in 1p31.2, 10q11.21, 12p13.1, 16q23.1-q23.2, 17p13.3, 17q21.31, and 21q21.2. Additionally, a high percentage of cases showed LOH at 6p25.1-p25.3 (75%), 8p22-p23.2, and 10q22.1 (70%). Several tumor suppressor genes (TSGs) have been mapped in these loci. These results demonstrate that the HuSNP mapping assay can serve as an alternative to comparative genomic hybridization for assessing genome-wide LOH and can identify chromosomal regions harboring candidate TSGs implicated in prostate cancer.     

Immunohistological detection of BRAF25 in human prostate tumor and cancer specimens

BRAF25 is an alternatively spliced protein of BRAF35 (see associated paper). We have mapped the BRAF25 gene to chromosome sub-band 19p13.3, a region where loss of chromosomal heterozygosity has been reported in about 50% of ovarian cancers. Because of the high incidence of genetic links of prostate cancer to breast and ovarian cancers, we investigated the BRAF25 expression in the prostate specimens. Immunohistochemical analysis using antibodies specific for BRAF25 revealed a strong immunostaining in sections of the benign prostatic hyperplasia (BPH). The staining was concentrated on the nuclei of cells facing the lumen of prostatic glands, even though the sporadic nuclei of cells in stromas were also stained. However, the expression of BRAF25 was dramatically reduced in intermediate prostate cancer and absent in advanced prostate cancer. Preincubation of the antibody with the immunizing peptide abolished immunostaining in BPH specimens. Therefore, the expression of BRAF25 was gradually lost in prostate cancer.     

Optimization of prostate cancer cell detection using multiplex tyramide signal amplification

Approximately 29 000 men die of prostate cancer (PCa) each year in the United States, and 90% to 100% of them are due to incurable bone metastasis. It is difficult to determine (1) when PCa disseminates in the natural history of the disease; (2) where cancer cell disseminates before becoming overt metastatic lesions; and (3) which tumors are aggressive and which are indolent. Tumor tissue and liquid (blood and bone marrow) biopsies provide important information to answer these questions, but significant limitations exist for immunostaining strategies that assess protein expression in these tissues. Classic immunohistochemistry (IHC) assays can typically assess expression of one or two proteins per tissue section. We have developed a novel immunofluorescence staining protocol to detect a panel of seven proteins on PCa tissue from primary tumor biopsies and metastatic lesion autopsy tissue, as well as cancer cells from liquid biopsies. We used a tyramide-based system to amplify the true signal and optimized the protocol to reduce background signal, thereby boosting the signal-to-noise ratio. Any protein-specific antibody in this protocol can be exchanged for a different validated antibody. This protocol therefore, represents a highly informative and flexible assay that can be used to provide important information about cancer tissue for the purpose of improving detection, diagnosis, and treatment.     

Evaluation of the effectiveness of transurethral radio frequency hyperthermia in the canine prostate: temperature distribution analysis

The heating pattern of a transurethral radio frequency (RF) applicator and its induced steady-state temperature field in the prostate during transurethral hyperthermia treatment were investigated in this study. The specific absorption rate (SAR) of the electromagnetic energy was first quantified in a tissue-equivalent gel phantom. It was used in conjunction with the Pennes bioheat transfer equation to model the steady-state temperature field in prostate during the treatment. Theoretical predictions were compared to in vivo temperature measurements in the canine prostate and good agreement was found to validate the model. The prostatic tissue temperature rise and its relation to the effect of blood perfusion were analyzed. Blood perfusion is found to be an important factor for removal of heat especially at the higher RF heating level. To achieve a temperature above 44 degrees C within 10 percent of the prostatic tissue volume, the minimum RF power required ranges from 5.5 W to 36.4 W depending on the local blood perfusion rate (omega = 0.2-1.5 ml/gm/min). The corresponding histological results from the treatment suggest that to obtain better treatment results, either higher RF power level or longer treatment time (> 180 minutes) is necessary. This is consistent with the predictions from the theoretical model developed in this study.     

Quantum dot-based protein micro- and nanoarrays for detection of prostate cancer biomarkers

In this article, we demonstrate the fabrication and detection of cancer protein biochips consisting of micro- and nanoarrays whereby pegylated quantum dots (QDs) conjugated to antibodies (Abs) of prostate specific antigens (PSA) were used for the detection of clinical biomarkers such as PSA. BSA which acts as an efficient blocking layer in microarrays, tends to show an interaction with QDs. In view of this fact, we investigated two series of samples which were fabricated in the presence and absence of BSA blocking layer. Variation in the incubation time required for the antigen-antibody interaction to take place, different proteins as controls and the effect of bare QDs on these microarrays, were the three main parameters which were studied in these two series. Samples fabricated in the absence of BSA blocking layer exhibited an extremely high specificity in the detection of cancer proteins and were also marked by negligible nonspecific binding effects of QDs, in stark contrast to the samples fabricated using BSA as a blocking layer. Fabrication of nanoarrays of QD-conjugated PSA Abs having a spot size of nearly 900 nm has also been demonstrated. Thus, we show the potential offered by QDs in in vitro analysis of cancer biomarker imaging.     

Radiation therapy failure in prostate cancer patients: risk factors and methods of detection

Radiation therapy for clinically localized prostatic carcinoma remains one of the mainstays among therapeutic approaches; however, patients continue to fail radiation therapy at too high a rate. This article reviews the risk factors and methods of detection for prostate cancer recurrence. The relative merits of the three major pre-therapy prognostic indicators-TNM staging, Gleason score, and serum prostate-specific antigen (PSA) levels-are discussed. The use of staging and Gleason score, as well as digital rectal examination, transrectal ultrasound, and post-radiation prostate biopsies in detecting failure of radiation therapy is reviewed. Challenges relating to the use of serum PSA levels as an indicator of recurrence are examined. Finally, this article makes recommendations as to procedure for evaluating patients suspected of failing radiation therapy.     

Value of intraoperative ultrasonography in tonsil cancer

Background

The exact assessment of a tonsil carcinoma''s size is often difficult because of the tumour''s submucosal extension and deep infiltration.

Aim

The aim of the study is to assess the usefulness of intraoperative ultrasonography in tonsil cancer.

Material

Twenty patients with carcinoma of the tonsil were included in the study (squamous cell carcinoma keratosis – 12, squamous cell carcinoma akeratosis – 6, diffuse large B cell lymphoma – 1, neoplasma malignum microcellulare – 1).

Method

Transcutaneous, endoscopic, and intraoperative ultrasonography were performed using a linear 7.5 MHz probe.

Results

The difference in the results was statistically significant between palpation examination and intraoperative ultrasonographic examination, between transcutaneous ultrasonographic examination and intraoperative ultrasonographic examination, and between endoscopic ultrasonographic examination and intraoperative ultrasonographic examination in tonsil tumours. Generally, tumour size assessed by intraoperative ultrasonography was more advanced than those assessed by other methods.

Conclusions

Intraoperative ultrasonography is a safe, non-invasive method, which can be repeated at every stage of surgery. There were no contraindications or side effects. In all cases histological margins corresponded to sonographic margins. Intraoperative ultrasonography provides a quick and reliable orientation during resection of tonsil carcinoma.     

A specific molecular beacon probe for the detection of human prostate cancer cells

The small-molecule, water-soluble molecular beacon probe 1 is hydrolyzed by the lysate and living cells of human prostate cancer cell lines (LNCaP), resulting in strong green fluorescence. In contrast, probe 1 does not undergo significant hydrolysis in either the lysate or living cells of human nontumorigenic prostate cells (RWPE-1). These results, corroborated by UV-Vis spectroscopy and fluorescent microscopy, reveal that probe 1 is a sensitive and specific fluorogenic and chromogenic sensor for the detection of human prostate cancer cells among nontumorigenic prostate cells and that carboxylesterase activity is a specific biomarker for human prostate cancer cells.