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PubMed1999

Prognostic significance of beta-microseminoprotein mRNA expression in prostate cancer.

BACKGROUND: Human beta-microseminoprotein (beta-MSP or PSP94) is a small protein secreted by prostatic epithelial cells. We recently reported the presence of low levels of beta-MSP mRNA expression and protein in most prostate cancer tissues. METHODS: Beta-MSP and mRNA expression was examined by in situ hybridization in biopsy specimens obtained from 92 patients with prostate cancer. All tissue specimens were obtained by needle biopsies prior to treatment. All patients subsequently received endocrine therapy. To estimate the influence of beta-MSP mRNA expression and three possible prognostic factors, i.e., patient age, clinical stage, and Gleason score, on time to progression under endocrine therapy, univariate and multivariate analyses were performed using Cox's proportional hazards regression model. RESULTS: Multivariate survival analysis showed that clinical stage was the strongest prognostic factor (P = 0.006) and that beta-MSP mRNA expression was the second strongest factor (P = 0.038) in 92 patients with stage B-D disease. Analysis of only 51 patients with stage D disease showed that beta-MSP mRNA expression was the only significant prognostic indicator for progression under endocrine therapy (P = 0.003). CONCLUSIONS: The presence of cells that express the beta-MSP transcript may be a novel indicator of potentially aggressive prostate cancer.

Aged↗
PubMed1999

In situ hybridization study of PSP94 (prostatic secretory protein of 94 amino acids) expression in human prostates.

BACKGROUND: The prostatic secretory protein of 94 amino acids (PSP94), also named beta-microseminoprotein, is one of the major proteins secreted by the human prostate. However, its value as a prognostic marker for prostate cancers is still under debate. The aim of the present study was to examine the expression pattern of this protein in fetal, pubertal, and aged human prostates. METHODS: Nonisotopic in situ hybridization using a digoxigenin-labeled riboprobe for PSP94 and immunohistochemistry were used to demonstrate the expression of PSP94 in different regions or zones of fetal, pubertal, and adult human prostates. Its localization pattern was also compared with those of two other major secretory proteins, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), by immunohistochemistry. RESULTS: PSP94 mRNA and its protein were localized to the secretory epithelium of normal pubertal and adult human prostates. No hybridization signal and immunoreactivity of PSP94 were seen in fetal prostates at 6-7 months of gestation, whereas some glandular cells were positive to PSA and PAP immunostainings. In the adult prostates, PSP94 expression was intense in the acini in the peripheral zone, less intense in the transition zone, and variable in the central zone. Such a zonal expression pattern was more apparent in the pubertal prostates. However, no obvious differential expression pattern was observed in the immunohistochemistry of PAP and PSA, which showed a uniform staining of the secretory epithelia of the acini in all anatomic zones. The hybridization signals and immunoreactivity of PSP94 became reduced or lost in premalignant prostatic intraepithelial neoplastic lesions and different grades of prostatic carcinomas. CONCLUSIONS: Fetal prostates at 6-7 months of gestation already synthesize PSA and PAP but not PSP94. The delayed expression of PSP94 appears to correlate with the development of the prostate gland. A differential expression pattern of PSP94 is demonstrated in different anatomical zones, showing that this protein is more expressed and synthesized in the acini in the peripheral zone than in the central and transition zones. However, such a zonal pattern is not seen in the immunohistochemistry of PSA and PAP. The present study also shows that PSP94 is downregulated in different grades of prostate cancers.

Adolescent↗
PubMed1997

Detection of prostate carcinoma using prostate specific antigen, its density, and the density of the transition zone in Japanese men with intermediate serum prostate specific antigen concentrations.

BACKGROUND: This study was undertaken to determine whether the prostate specific antigen (PSA) density (PSAD) and PSAD of the transition zone (PSADT) are useful in the detection of prostate carcinoma in Japanese men with intermediate levels of serum PSA. METHODS: Two hundred and eighty-seven Japanese men with intermediate serum PSA levels (2.1 ng/mL to 10 ng/mL) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and systematic biopsy under TRUS guidance. The volume of the transition zone was also measured by TRUS in 134 patients. The PSAD and PSADT were determined for each patient, and their relationship to prostate carcinoma detection was examined. RESULTS: Prostate carcinoma was detected in 30 of 287 patients (10.5%). Although the serum PSA levels were similar in patients with benign and malignant prostate disease (P = 0.541), the prostate volume (P 0.0009) and PSAD (P < 0.0001) differed significantly in the two groups; in the patients with prostate carcinoma, the prostate volume was smaller, and the PSAD higher, than in the patients with benign disease. At the PSAD cutoff value of 0.18 ng/mL/cm3 or greater, the sensitivity was 70% and the specificity was 67% for the diagnosis of prostate carcinoma. The PSAD was found to be significantly better in the differentiation between benign and malignant prostate disease than the serum PSA in the receiver operating characteristic analyses (P = 0.045). However, the receiver operating characteristic curve for PSAD was not significantly different compared with that for PSA in the men with negative digital rectal examination findings. Prostate carcinoma was detected in 9.0% (12 of 134) of the patients who underwent PSADT determination. Receiver operating characteristic analyses showed that PSADT was not superior to PSA in the detection of prostate carcinoma. CONCLUSIONS: In Japanese men with intermediate serum PSA concentrations, PSAD offers additional information useful in the detection of prostate carcinoma, but PSADT does not. Although use of PSAD may decrease the number of unnecessary biopsies, a significant number of prostate carcinomas may be overlooked. Therefore, the authors recommend that serum PSA levels continue to be used as an indicator for biopsy in Japanese men.

Adult↗
PubMed2000

The annual report to the nation on the status of cancer, 1973-1997, with a special section on colorectal cancer.

BACKGROUND: This annual report to the nation addresses progress in cancer prevention and control in the U.S. with a special section on colorectal cancer. This report is the joint effort of the American Cancer Society, the National Cancer Institute (NCI), the North American Association of Central Cancer Registries (NAACCR), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS). METHODS: Age-adjusted rates were based on cancer incidence data from the NCI and NAACCR and underlying cause of death as compiled by NCHS. Joinpoint analysis was based on NCI Surveillance, Epidemiology, and End Results (SEER) program incidence rates and NCHS death rates for 1973-1997. The prevalence of screening examinations for colorectal cancer was obtained from the CDC's Behavioral Risk Factor Surveillance System and the NCHS's National Health Interview Survey. RESULTS: Between 1990-1997, overall cancer incidence and death rates declined. Joinpoint analyses of cancer incidence and death rates confirmed the declines described in earlier reports. The incidence trends for colorectal cancer have shown recent steep declines for whites in contrast to a leveling off of the rates for blacks. State-to-state variations occurred in colorectal cancer screening prevalence as well as incidence and death rates. CONCLUSIONS: The continuing declines in overall cancer incidence and death rates are encouraging. However, a few of the top ten incidence or mortality cancer sites continued to increase or remained level. For many cancer sites, whites had lower incidence and mortality rates than blacks but higher rates than Hispanics, Asian and Pacific Islanders, and American Indians/Alaska Natives. The variations in colorectal cancer incidence and death rates by race/ethnicity, gender, age, and geographic area may be related to differences in risk factors, demographic characteristics, screening, and medical practice. New efforts currently are underway to increase awareness of screening benefits and treatment for colorectal cancer.

Breast Neoplasms↗
PubMed1997

Chemoprevention: will it work?

Cancer chemoprevention has been a major area of inquiry in the United States for over a decade. The field originated from the confluence of developments in laboratory carcinogenesis and nutritional epidemiology. Although still owing much to other research disciplines, chemoprevention researchers have developed models and methodologies specific to the topic. Of particular importance has been the search for intermediate endpoints which might provide valid indications of cancer prevention effectiveness. Intermediate endpoints, however, suffer the limitations of the extrapolation required to the prevention of cancer per se. More direct evidence of chemoprevention effectiveness may come from trials that use actual reduction of cancer incidence as the primary endpoint. Several trials of potential chemopreventive agents are underway or have been completed in the United States or elsewhere with U.S. investigator participation. The results to date have been mixed, and unanticipated findings have raised doubts about the probability of success of primary prevention of cancer by chemoprevention. Future prospects for success may depend upon development of a better understanding of biological mechanisms before progressing to large, long-duration human population trials.

Anticarcinogenic Agents↗
PubMed1999

Genetic predisposition, environment and cancer incidence: a nationwide twin study in Finland, 1976-1995.

Twin studies integrate genetic and environmental (including physical environment and life-style) information by comparing monozygotic and dizygotic twins for the occurrence of disease. Our objectives were to compare cancer incidence in twins with national rates and to estimate both the probability that co-twins of affected twins may develop cancer and the importance of genetic predisposition and environment in cancer development. The nationwide record linkage of the Finnish Twin Cohort Study, the Finnish Cancer Registry and the Central Population Register allowed the follow-up of 12,941 same-sexed twin pairs for incident primary cancers from 1976 to 1995. Zygosity was determined by use of a validated questionnaire in 1975. Methods included calculation of standardized incidence ratios and concordances and fitting of structural equation models. A total of 1,613 malignant neoplasms occurred in the cohort. The overall cancer incidence among twins resembled that among the general population. Monozygotic co-twins of affected twins were at 50% higher risk than were dizygotic co-twins. Based on genetic modeling, inherited genetic factors accounted for 18% (95% confidence interval 4-32%) of the liability in inter-individual variation in the risk of overall cancer, while non-genetic factors shared by twins accounted for 7% (0-16%) and unique environmental factors for 75% (65-85%). Our results appear to exclude a contribution greater than one-third for genetic predisposition in the development of cancer in the general population, thus pointing to the earlier confirmed substantial role of environment.

Adult↗
PubMed1998

Diagnostic dilemmas in the interpretation of fine-needle aspirates of granulomatous prostatitis.

We have reassessed the fine-needle aspirates of ten cases previously diagnosed as granulomatous prostatitis (GP). Presence of unequivocal epithelioid granulomas (EG) or typical caseous necrosis was required for a smear to be diagnosed as nonspecific granulomatous prostatitis (NGP) or tuberculous prostatitis (TP), respectively. As a consequence only six cases met the criteria set up for the diagnosis of NGP and two for TP. The purpose of this revision was fourfold: to find out if there are other prostatic conditions which may be confused with GP cytologically, to investigate if there is a single cytologic finding that permits a confident diagnosis of GP, to find out if the etiology can be suggested on cytologic grounds alone, and, finally, to assess if carcinoma can be ruled out safely. We conclude the following: 1) There are various prostatic conditions which share some cytologic findings with GP; 2) the presence of distinct EG is the hallmark criterion of GP; 3) NGP and TP can be safely diagnosed cytologically but other forms of GP would require additional clinical data and ancillary techniques; and 4) carcinoma can be safely distinguished from GP cytologically. To succeed in this task the cytopathologist must diagnose carcinoma only if clear-cut carcinoma cells are present and must be aware of the reactive changes induced by the inflammatory infiltrate both in duct/acinar and metaplastic cells.

Aged↗
PubMed1999

Serum bound forms of PSP94 (prostate secretory protein of 94 amino acids) in prostate cancer patients.

PSP94 (prostate secretory protein of 94 amino acids) was regarded as a possible prostate cancer marker, however, it has been controversial. All prior studies were designed to test the free form in serum using antibodies to PSP94. Results presented here demonstrate that PSP94 exists in prostate cancer patients in two forms, free and bound, and that the majority is present as serum bound complexes. This result was demonstrated by using both native and SDS-PAGE analyses of serum proteins from prostate cancer patients. Chromatographic separation of serum total proteins by a molecular sieve column generated two peaks (peak I and II), which were reactive with rabbit antiserum to human PSP94 in Western blot experiments. Peak I was eluted before the IgG fraction at a molecular weight larger than 150 kDa, and peak II appeared after serum albumin ( approximately 67 kDa) was eluted. By using a biotinylated PSP94 as an indicator of the free form of PSP94, we demonstrate that peak I contains serum PSP94-bound complexes and peak II is likely the free form of serum PSP94. Since the molecular weight of serum PSP94-bound complexes is close to IgG during molecular sieve separation, serum PSP94 complexes were further purified through two rounds of protein A column separation, followed by DEAE-ion exchange column chromatography. In vitro dissociation tests of the purified PSP94-bound complexes showed that the binding of serum PSP94-complexes is probably via disulfide bonds and is chemically stable. The results presented here indicate that serum PSP94-bound complexes must be considered in evaluating the clinical utility of PSP94 as a prostate cancer marker.

Antibodies↗
PubMed1975

Metastases to the vertebral column.

Review of 643 autopsies revealed 374 cases of malignant neoplasms, of which 140 were found to have evidence of disease metastatic to the vertebral bodies of the thoracolumbar spine. A comparison is made of the proportion of cases detected by clinical radiographs antemortem vs. the cases of metastatic tumor of the spine detectable by radiographs of slabs of the spine and by histologic examination. A high degree of correlation was found between metastases detected by fine-detail radiography and those detected by microscopic examination. Thus, the incidence of neoplastic metastases to the thoracic and lumbar vertebral bodies is presented, and the reliability of fine-detail radiography is assessing the presence of neoplastic metastases at autopsy is indicated.

Autopsy↗
PubMed1976

Laboratory aids to diagnosis--enzymes.

A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.

Acid Phosphatase↗