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p27(kip1) and Other Cell-Cycle Protein Expression in Normal and Neoplastic Endocrine Tissues.

Endocrine tumors are often diagnostic challenges. Recent studies have suggested that proteins that regulate cell cycle may have diagnostic and prognostic utility in endocrine tumors. p27(kip1) (p27) is a cyclin-dependent kinase inhibitor that regulates the transition from the G1 to the S phase of the cell cycle. p27 and other cell-cycle proteins are becoming increasingly important in assessing the biologic behavior of endocrine neoplasms, classifying hyperplastic and neoplastic endocrine tissues, and in the progression of endocrine tumors. p27 appears to separate normal from neoplastic endocrine tissues and, in some cases, benign from malignant endocrine tumors. However, there is overlap in p27 expression among individual cases of benign and malignant tumors, and p27 has only limited prognostic utility in endocrine tumors compared to some epithelial tumors such as breast and prostate neoplasms. Thus, more effective molecular and cellular markers that can be used for diagnostic and prognostic purposes in endocrine pathology are needed.

Journal Article↗

[Malignant mesothelioma--a diagnostic challenge].

Malignant mesothelioma is a rare neoplasm associated, in 80% of the cases, with exposure to asbestos fibres, with a latency period between 20 and 50 years. The treatment is palliative in most cases because of the extension of the disease at the time of diagnosis. Mesothelioma is a resistant tumour to chemotherapy and radiotherapy. Overall survival varies between 4 and 18 months, rarely over 5 years. The authors present a case of a 82-year-old man, ex-sailor, with prostatic neoplasm in hormonal "escape" phase, admitted with cough and dyspnea. The chest radiograph showed extensive right pleural effusion. The diagnostic hypothesis were metastatic, infectious and primitive neoplasm origin. Pleural biopsy revealed epithelial malignant mesothelioma confirmed by thoracoscopy, associated with prolongated occupational exposure to asbestos fibres. Without surgery indication the patient was submitted to chemotherapy with gencitabin and cisplatin associated with pleurodesis. Although he improved clinically, the presence of two malignant neoplasms, a rare situation in clinical practice, is associated with a poor prognosis, especially condicionated by the epithelial malignant mesothelioma in Butchart stage II. Finally, we discussed new differential diagnostic techniques with metastatic adenocarcinoma and target therapies under study.

Aged↗

Trends in cancer mortality in Argentina, 1966-91.

Trends in death certification rates for 12 major cancer sites and total cancer mortality in Argentina were analysed for the period 1966-91 on the basis of the World Health Organization database. In the late 1960s, total cancer mortality rates in Argentina (184/100,000 men, 117/100,000 women, world standard) were among the highest in the world. Over the 25-year period considered, however, cancer mortality in Argentina declined by 15% in both sexes, to reach 157/100,000 in men and 99/100,000 in women, for 1990-91. These rates were somewhat lower than those of North America and, particularly for women, relatively low on a worldwide scale. The favourable trends, observed mostly between the 1960s and the 1980s, reflect the steady decline in gastric cancer rates in both sexes, together with some decline in oesophageal, lung and other tobacco-related neoplasms, mostly in men, following some decline in tobacco consumption over the last two decades. The fall in oesophageal cancer may be related to decreased consumption of hot maté, too. Colorectal cancer rates were high in the 1960s, but declined by 17% in men and 35% in women. An approximately 50% decline was observed for skin cancer mortality, which was among the lowest in the world in the early 1990s, and some decline was observed also for leukaemias and uterine cancer, while breast and prostate neoplasms showed a general stability. The two major unfavourable features of cancer mortality in Argentina were the persistently high rates for oesophageal in men, and for uterine cancer mortality in women. These are likely a result of hot maté drinking for oesophageal cancer and inadequate screening for cervical cancer.

Age Distribution↗

Epithelial-stromal tumor of the seminal vesicles in the transgenic adenocarcinoma mouse prostate model.

The transgenic adenocarcinoma mouse prostate (TRAMP) model, designed for researching human prostatic cancer, was genetically engineered to harbor a transgene composed of the simian virus 40 Large-T/small-t antigen promoted by the rat probasin gene. In addition to prostatic neoplasms, the TRAMP mouse develops tumors in the seminal vesicles. This study was conducted to evaluate the pathology and histogenesis of TRAMP seminal vesicle neoplasms. Tissues of accessory sex organs harvested from 72 TRAMP mice of various ages (11-40 weeks of age) were fixed in neutral buffered formalin and stained with hematoxylin and eosin, desmin, 5-bromo-2'-deoxyuridine (BrdU, treated animals only), and SV40 Large-T antigen (SV40-Tag). In the seminal vesicles, we found neoplastic stromal cells that emerged multicentrically just beneath the epithelium, densely packed between the epithelium and the smooth muscle layer. These stromal cells frequently exhibited mitotic figures and showed BrdU incorporation and SV40-Tag protein expression in the nuclei and immunopositivity for desmin. The proliferative mesenchymal cells were lined by cuboidal to columnar epithelium. Some of the larger papillary, polypoid lesions exhibited a phyllodes pattern resembling that seen in mixed epithelial-stromal tumors of the breast, prostate, and seminal vesicles of humans. Although the epithelium was negative for SV40-Tag and showed only occasional incorporation of BrdU, it clearly participated in the biphasic proliferation, forming papillary, cystic, and tubuloglandular structures. No conclusive evidence of malignancy (invasion or metastasis) was identified. Our recommended diagnosis of this lesion in the seminal vesicles is epithelial-stromal tumor.

Animals↗

Effectiveness of ultrasound in the preoperative evaluation of patients with prostatism.

To avoid the disadvantages of intravenous urography (IVU) and urethrocystoscopy (UCS), we investigated prospectively their replacement by ultrasound, performed during one visit in the outpatient department, in the evaluation of patients with symptoms of prostatism. One hundred twenty patients (aged 44-89 years) were included in this study. All patients underwent two main diagnostic procedures: ultrasound of the kidneys and bladder and transrectal ultrasound of the prostate (procedure A1). This was compared with IVU and UCS (procedure A2). Following procedure A1, the main diagnoses made were benign prostatic hypertrophy in 84 patients, prostatitis in 24 patients, and prostatic cancer in 12 patients. By following procedure A2, the diagnosis was changed in 20 cases. Fourteen patients had a bladder neck sclerosis, and six had a urethral stricture. There was no relevant diagnostic difference between IVU and ultrasound of the kidneys and bladder. Ultrasound of the prostate gives better information on prostatic abnormalities than does IVU or UCS. A patient with prostatism can be screened completely during one visit at the outpatient department. Only for detection of bladder neck sclerosis and urethral strictures does UCS remain preferable.

Aged↗

Transrectal longitudinal ultrasonotomography of the prostate by electronic linear scanning.

Transrectal longitudinal ultrasonotomography of the prostate with the newly developed electronic linear scanning method was done on 100 cases and the characteristic echo patterns for each prostatic disease were obtained. With this method we can observe real-time longitudinal tomograms of the prostate, seminal vesicles and bladder. Real-time observations make it easier to examine the relationship between the prostate and its surrounding organs, especially the bladder neck and the prostatic urethra, at the time of urination.

Adult↗

Prostate-specific membrane antigen is undetectable in choroidal neovascular membrane.

BACKGROUND: Choroidal neovascular membrane (CNVM) is one of the leading causes of severe visual loss and is often associated with age-related macular degeneration (AMD). Various modalities of treatment, including photocoagulation and surgery, are being considered as options, but with limited success. Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein expressed in benign and malignant prostatic tissues, in some non-prostatic tissues, and in the endothelium of tumor-associated neovasculature of non-prostatic neoplasm. Some studies have suggested that the expression of PSMA is restricted to endothelium from tumor-associated neovasculature and might be stimulated by some tumor-secreted angiogenic factors. However, no previous study demonstrating PSMA expression in non-related tumor neovasculature, such as CNVM, has been performed to date. Furthermore, demonstration of PSMA expression in CNVM in AMD patients could reveal a novel target for antineovascular therapy. The purpose of this study was to evaluate the immunohistochemical expression of PSMA in CNVM from AMD. METHODS: Immunohistochemical analysis, with a standard avidin-biotin complex technique, was performed using an anti-PSMA mouse monoclonal antibody in 30 specimens of surgically excised CNVM from AMD patients. Antibody to an endothelial cell specific marker, factor VIII, was used to confirm the location of the endothelial cells. RESULTS: The angiogenic microvessels of the 30 cases demonstrated negative staining to PSMA while factor VIII was expressed in all cases. Seventy-five percent of the secretory-acinar epithelium of the prostatic hyperplasia specimen stained positive, confirming that the immunohistochemical technique was correctly performed. CONCLUSION: The absence of PSMA expression in non-tumoral neovasculature supports the theory, previously suggested, that endothelial cell PSMA expression may be stimulated by one or more tumor-secreted angiogenic factors. Angiogenesis is very important in neoplasia and the endothelial expression of PSMA in tumor-associated neovasculature may represent a target for antineovasculature-based therapy. The absence of PSMA expression in CNVM suggests that PSMA may not be a potential target for antineovasculature-based therapy.

Journal Article↗

The application of age, period and cohort models to predict Swiss cancer mortality.

In order to project trends in mortality from 11 major cancer sites in Switzerland to the end of the current century, a log-linear Poisson age/period/cohort model with arbitrary constraints on the parameters was used, fitted to the observed rates for the period 1950-84. One projection was based on the assumption of a total absence of change in the effect of period, the second was based on a linear extrapolation of the logarithms of the seven known periods, and the third was related to a series of a priori external epidemiological hypotheses, whenever available. For instance, coefficients below unity were used for lung and other tobacco-related neoplasms in men, since some decline in exposure to tobacco carcinogens was observed among Swiss men, and above unity for women since the prevalence of smoking has risen among successive generations of women. Although the method has limitations and uncertainties, several qualitative indications could be derived from this exercise. For instance, the various models suggest that the age-standardized mortality from oral cancer in men will probably increase up to the end of the century, even under the optimistic assumption of an appreciable decline in smoking, while cancer of the oesophagus is likely to level-off around current values, as other tobacco-related neoplasms, prostate cancer in men, and breast cancer in women will probably do. Some steady decline is predicted by various models fitted to the incidence of stomach and intestinal cancer in both sexes, and to ovarian cancer. Lung cancer will continue to rise in women but will stop rising in men, and it will possibly fall if the hypothesis of a decline in exposure to tobacco carcinogens proves correct. Although any prediction has, by definition, substantial difficulties and uncertainties, projections of cancer mortality in the near future are based on a substantial amount of information already available, and may offer valuable information for epidemiological inferences and health planning purposes.

Adult↗

Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528,693 adults.

BACKGROUND: It is unclear how frequently unprovoked venous thromboembolism (VTE) reflects the presence of an occult cancer. METHODS: The California Cancer Registry was used to identify diagnosed cases of 19 common malignancies during a 6-year period. Cases were linked to a hospital discharge database to identify incident VTE events in the year before the cancer diagnosis date. The standardized incidence ratio (SIR) of unprovoked VTE was determined by using the age-, race-, and sex-specific incidence rates in California. RESULTS: Among 528,693 cancer cases, 596 (0.11%) were associated with a diagnosis of unprovoked VTE within 1 year of the cancer diagnosis, compared with 443.0 expected cases (SIR, 1.3; 95% confidence interval, 1.2-1.5; P<.001). Among cases with metastatic-stage cancer, the SIR was 2.3 (95% confidence interval, 2.0-2.6; P<.001), whereas for all other stages, the SIR was 1.07 (95% confidence interval, 0.97-1.18; P = .09). The incidence of preceding VTE was increased over that expected only during the 4-month period immediately preceding the cancer diagnosis date (P<.001). Only 7 cancer types were associated with a significantly elevated SIR: acute myelogenous leukemia; non-Hodgkin lymphoma; and renal cell, ovarian, pancreatic, stomach, and lung cancer (SIR range, 1.8-4.2). CONCLUSIONS: In the year preceding the diagnosis of cancer, the number of cases with unprovoked VTE was modestly higher than expected, and almost all of the unexpected VTE cases were associated with a diagnosis of metastatic-stage cancer within 4 months. Given the timing and advanced stage of the unexpected cases, it is unlikely that earlier diagnosis of these cancers would have significantly improved long-term survival.

Adult↗

Efficient cell segmentation tool for confocal microscopy tissue images and quantitative evaluation of FISH signals.

In this paper we have presented a semi-automatic method for segmenting 3-D cell nuclei from tissue images obtained using Confocal Laser Scanning Microscope. This microscope can focus at different layers of the specimen and hence a stack of images giving a 3D representation can be obtained. The existing methods for segmenting the cells in 3-D confocal images are highly interactive and, hence, time consuming. We have developed an approach, where, given one segmented image-slice (optical section) of the set of confocal images, the remaining image-slices in the image stack can be automatically segmented in a layered approach. One of the image-slices in an image stack is considered as a representative image-slice. In this image-slice, overlapping boundary pixels are identified interactively while the remaining part of the cell boundary is marked using Laplacian of a Gaussian operator. This interactively traced portion of the boundary is considered as initial boundary for finding the overlapping boundary pixels in the neighboring image-slices. Simple basic search strategy is used for boundary search in the neighboring image-slices. The method minimizes the human interaction and is also found to be efficient and reasonably accurate. Some experimental results are presented to illustrate the usefulness of the technique. We have also given the application of our segmentation method to quantitative evaluation of fluorescence in situ hybridization (FISH) signals. A brief comparative study of visual FISH signal evaluation and the FISH signal counting by automatic image analysis is also given.

Automation↗

Identification of binding proteins for PSP94 in human prostate adenocarcinoma cell lines LNCaP and PC-3.

BACKGROUND: Prostatic secretory protein of 94 amino acids (PSP94) is one of the predominant proteins found in human seminal fluid. Limited information is available regarding a physiological function for PSP94. An important step in the elucidation of this function is the determination of the mechanism of interaction of PSP94 with potential cellular targets. METHODS: Equilibrium binding assay was employed to demonstrate specific binding of biotinylated-PSP94 to the LNCaP and PC-3 cell lines. Binding proteins were partially purified by PSP94 affinity-chromatography from LNCaP, PC-3 cells, and prostate tissues. RESULTS: Binding of biotinylated-PSP94 to LNCaP and PC-3 cells was saturable and time and temperature dependent. The binding could be specifically competitively inhibited by unlabelled PSP94. Two types of PSP94 binding sites with distinct affinity (Kd) and density (Bmax) were determined by Scatchard analysis for each of the two cell lines. For the LNCaP cells, these values were Kd 1 = 0.75 nM and Bmax1 = 300 fmol/mg protein and Kd 2 = 4.5 nM, Bmax2 = 780 fmol/mg protein, respectively. Similar affinity and density results were obtained for PC-3 cells: Kd 1 = 0.83 nM, Bmax1 = 250 fmol/mg protein, and Kd 2 = 5.0 nM, Bmax2 = 700 fmol/mg. The binding of biotinylated-PSP94 to the LNCaP cells was competitively inhibited by the partially purified proteins. Analysis of these proteins SDS-PAGE showed three main bands and the molecular weights of these three bands were approximately 180, 100 and 60 kD, respectively. CONCLUSIONS: The data showed the presence of specific binding proteins to the PSP94 in LNCaP, PC-3 cells, and prostate tissue.

Adenocarcinoma↗