Expression of prostate-specific antigen variant MRNA transcripts in prostate cancer and benign prostatic hyperplasia

Prostate-specific antigen (PSA) is important in tumour detection, monitoring disease progression and tumour recurrence. however, PSA is not a cancerspecific marker as levels can also be elevated in benign prostatic disease. A number of different mRNA transcripts of PSA have also been identified in prostatic tissue, but have not been fully characterized (PSA 424, PSA 525, Schulz transcript). Tissue specimens from transurethral resection of the prostate (TURP) or radical prostatectomy were obtained from 17 men with BPH and 15 men with prostate cancer. Total RNA was extracted, and reverse-transcriptionpolymerase chain reaction (RT-PCR) and Southern analysis carried out using transcript-specific primers and probes to determine which mRNA PSA transcripts were expressed. Real-time PCR was performed to determine transcript levels between the two groups using transcript-specific primers and SYBR green fluorescence. Values obtained were normalized to a standard housekeeping gene, B2-microglobulin. Transcripts amplified by RT-PCR and real-time PCR were confirmed by DNA sequencing. Our results show that the transcripts were present in some, but not all, BPH and cancer samples indicating that they are not specific to either BPH or cancer. Analysis of real-time PCR normalized values using a Student’s t -test, shows that there is a significant difference between the two groups for PSA 424, but not wild-type PSA, PSA 525 or the Schulz transcript. Although a larger cohort of samples is needed to further confirm these results, these findings suggest that mRNA levels of PSA 424 may have some utility as a diagnostic or prognostic marker in prostate cancer detection.

Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer

BACKGROUND. Alterations of important protein pathways, including loss of prostate secretory granules, and disruption of the prostatic secretory pathway have been identified as early events in malignancy. In this study, proteomics was used to map the differences in protein expression between normal and malignant prostate tissues and to identify and analyze differentially expressed proteins in human prostate tissue with particular regard to the proteins lost in malignancy. METHODS. Small quantities of normal and malignant prostate tissue were taken fresh from 34 radical prostatectomy cases. After histological examination, proteins were solubilized from selected tissues and separated using two-dimensional electrophoresis. Using image analysis, the proteome of normal and malignant tissues were mapped and differentially expressed proteins (present in normal and absent in malignant tissue) were identified and subsequently analyzed using peptide mass finger printing and N-terminal sequencing. Western blotting and immunohistochemistry were performed to examine expression profiles and tissue localization of candidate proteins. RESULTS. Comparison of protein maps of normal and malignant prostate were used to identify 20 proteins which were lost in malignant transformation, including prostate specific antigen (PSA), alpha-l antichymotrypsin (ACT), haptoglobin, and lactoylglutathione lyase. Three of the 20 had not previously been reported in human prostate tissue (Ubiquitin-like NEDD8, calponin, and a follistatin-related protein). Western blotting confirmed differences in the expression profiles of NEDD8 and calponin, and immunohistochemistry demonstrated differences in the cellular localization of these two proteins in normal and malignant prostate glands. CONCLUSIONS. The expression of NEDD8, calponin, and the follistatin-related protein in normal prostate tissues is a novel finding and the role of these important functional proteins in normal prostate and their loss or reduced expression in prostate malignancy warrants further investigations. (C) 2002 Wiley-Liss, Inc.

Non-cancer mortality among people diagnosed with cancer (Australia)

Objective To investigate whether people diagnosed with cancer have an increased risk of death from non-cancer causes compared to the general population. Methods The non-cancer mortality of people diagnosed with cancer in Queensland (Australia) between 1982 and 2002 who had not died before 1 January 1993 was compared to the mortality of the total Queensland population, matching by age group and sex, and reporting by standardised mortality ratios. Results Compared to the non-cancer mortality in the general population, cancer patients (all cancers combined) were nearly 50% more likely to die of non-cancer causes (SMR = 149.9, 95% CI = [147-153]). This varied by cancer site. Overall melanoma patients had significantly lower non-cancer mortality, female breast cancer patients had similar non-cancer mortality to the general population, while increased non-cancer mortality risks were observed for people diagnosed with cervical cancer, colorectal cancer, prostate cancer, non-Hodgkin lymphoma and lung cancer. Conclusions Although cancer-specific death rates underestimate the mortality directly associated with a diagnosis of cancer, quantifying the degree of underestimation is difficult due to various competing explanations. There remains an important role for future research in understanding the causes of morbidity among cancer survivors, particularly those looking at both co-morbid illnesses and reductions in quality of life.