Search Results - (Author, Cooperation:R. Montironi)

2012-12-15

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Animals ; Castration ; Cell Line, Tumor ; Cohort Studies ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Male ; Methyltransferases/chemistry/genetics/metabolism ; Mice ; Mice, Inbred ICR ; Mice, SCID ; Oncogene Proteins/genetics/*metabolism ; Polycomb Repressive Complex 2/genetics/*metabolism ; Prostatic Neoplasms/genetics/*metabolism/mortality ; Protein Structure, Tertiary ; Receptors, Androgen/metabolism ; Xenograft Model Antitumor Assays

2018-04-19

BMJ Publishing Group

0021-9746

1472-4146

Medicine

1749-6632

Blackwell Publishing Journal Backfiles 1879-2005

Natural Sciences in General

Electronic Resource

1432-2307

Key words Serum prostate-specific antigen ; Prostate carcinoma ; Prostatic intraepithelial neoplasia ; Benign prostatic hyperplasia

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Serum prostate markers, in particular prostate-specific antigen (PSA), have truly revolutionised all aspects of the management of men with prostatic carcinoma (PCa), the most important application being related to its early detection and screening. Several studies have shown the clinical utility of PSA levels for staging patients with PCa, especially when associated with other parameters, such as tumour grade, digital rectal examination and transrectal ultrasound findings, to establish the likelihood of disease extension outside the gland and of positive lymph nodes. Also, serum PSA levels are useful in monitoring patients either after the initial diagnosis of PCa or following therapy.

Electronic Resource

1432-2307

Key words Renal parenchymal carcinoma ; Renal cell carcinoma ; Classification ; Staging ; Grading

Springer Online Journal Archives 1860-2000

Medicine

Abstract  The epithelial tumours of the adult kidney, in particular renal cell carcinoma (RCC), are a variety of neoplasms that can be classified by morphology and genotype. Although most are well characterised, typical and less typical tumour variants are recognised. There is evidence to indicate that stage is one of the most important prognostic factors, irrespective of tumour subtype. However, the appropriate handling of nephrectomy specimens is essential for accurate evaluation of diagnostic and prognostic factors in RCC. The problem of how to achieve more objective nuclear grading is still unresolved. The use of diagnostic decision support systems offers the possibility of a flexible approach to this problem, while still utilising morphological criteria. The histopathological analysis remains important, but new techniques of molecular and cell biology will be providing new tools of extraordinary power to sharpen the diagnosis and give it a biological interpretation.

Electronic Resource

1432-2307

Nucleoli ; Nucleolar margination ; Cytopathology ; Quantitative analysis

Springer Online Journal Archives 1860-2000

Medicine

Summary The diagnostic value of nucleolar margination, defined as the percentage of nucleoli touching the nuclear membrane, was investigated in 359 cytological preparations of benign and malignant lesions of the thyroid, breast, prostate and central nervous system. Premalignant lesions of the uterine cervix and non-invasive papillary carcinomas of the bladder were also examined. It was observed that the percentages in benign lesions were, in general, lower than in the malignant and that the values increased progressively with increasing grade in the cervix and bladder. When the overlap index was calculated, this gave exact information on the usefulness of nucleolar margination in distinguishing benign from malignant lesions, particularly in the prostate and thyroid and, to a lesser extent, in the breast and central nervous system. As for lesions of different grades, the calculation of the index allowed the identification of two subgroups, one corresponding to low grades (mild cervical dysplasia or urothelial papillary carcinoma of grade 1), the other subgroup to high grades (severe cervical dysplasia and carcinoma in situ, or papillary carcinoma of grade 3). Moderate dysplasia cases and grade 2 papillary carcinomas do not appear as separate intermediate categories but rather show values falling into the range of either the higher or lower grades. The margination values obtained from the cytological preparations corresponded well to those in the histological slides obtained from the resected specimens. In conclusion, nucleolar margination appears to be a feature which is easy to evaluate in a reproducible way and useful in cytological diagnosis.

Electronic Resource

1432-2307

Prostate ; Proliferating cell nuclear antigen ; Prostatic atrophy ; Benign prostatic hyperplasia ; Prostatic intra-epithelial neoplasia

Springer Online Journal Archives 1860-2000

Medicine

Abstract The expression and location of proliferating cell nuclear antigen (PCNA) immunostaining in epithelial, endothelial and stromal nuclei were assessed in prostatic intra-epithelial neoplasia (PIN). It was then compared with patterns in benign lesions and in invasive adenocarcinomas of the prostate. The PCNA-positive nuclei showed homogeneous or granular types of staining, or a mixture of both, and a gradation in the intensity of staining. Nuclei with granular and mixed patterns appeared lighter brown than those with a homogeneous pattern, which were darker and more often noted in PIN and invasive adenocarcinomas than in benign lesions. For epithelial PCNA-stained nuclei, the proportions in the two grades of PIN were greater than in benign prostatic hyperplasia (mean 3.16%, SE 0.31%) and prostatic atrophic ducts and acini (mean 0.56%, SE 0.09%), the values decreasing from the nuclei in the basal position towards those in the luminal layer. In grade 1, the category mean values were 9.51% (SE 1.14%) in the basal, 7.02% (SE 1.27%) in the intermediate and 6.02% (SE 0.90%) in the luminal position. In grade 2, the category mean values were 13.81% (SE 1.42%) in the basal position, 10.99% (SE 1.17%) in the intermediate and 7.91% (SE 1.43%) in the luminal position. In small and large acinar adenocarcinomas, the proportions of positive nuclei were 8.66% (SE 0.30%) and 9.06% (SE 0.30%), respectively. The category mean values in the cribriform adenocarcinomas were 14.40% (SE 0.61%) in the basal position, 11.84% (SE 1.30%) in the intermediate and 9.26% (SE 0.66%) in the luminal position. As in PIN, the proportions of immunostained nuclei in the adenocarcinoma with cribriform pattern decreased from the basal towards the luminal layer. In the solid/trabecular adenocarcinomas, the category mean value in the cell layer adjacent to the stroma was 17.60% (SE 2.92%), whereas in the other cell layers it was lower than that in the cells adjacent the stroma (mean 13.88%, SE 1.71%). For capillary endothelial and stromal cells, the percentages of PCNA-stained nuclei were much lower than those in the epithelial component. The lowest mean values were obtained in benign lesions, whereas the highest were in invasive adenocarcinomas, the percentages in PIN being intermediate.

Electronic Resource

1432-2307

Key words Prostate ; Mitogen-activated protein kinases ; Apoptosis

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Mitogen-activated protein (MAP) kinases are key elements of the signalling systems needed to transduce different extracellular messages into cellular responses. At least three parallel MAP kinase pathways have been identified: one, stimulated by serum and growth factors to activate extracellular signal-regulated protein kinases (ERKs) by dual tyrosine and threonine phosphorylation, triggers cell proliferation or differentiation; the other two, induced by a variety of cellular stresses to activate c-jun N-terminal kinases (JNKs) and reactivating kinase (p38/RK), result in growth arrest and induction of apoptosis. Mitogen-activated protein kinase phosphatases (MKPs) inactivate MAP kinases through dephosphorylation and, thus, can modulate the MAP kinase pathways. Expression of JNK-1, ERK-1, p38/RK and MKP-1 proteins was investigated by immunohistochemistry and expression of MKP-1 mRNA by in situ hybridisation in 50 cases of high-grade prostatic intraepithelial neoplasia (PIN), thought to represent the precursor of prostate cancer. The frequency of apoptotic cells was also determined in these cases. Overexpression of the three MAP kinases and MKP-1 mRNA was found in all cases of high-grade PIN compared with normal prostate. Immunoreactivity for MKP-1 protein was found to be as intense as in normal glands in 30% and weaker in 56% of the PIN cases. Fourteen per cent of PIN cases did not stain with MKP-1 antibody. The proportion of apoptosis was significantly higher (P 〈 0.008) in PIN lesions that did not express MKP-1 protein than in those that did. These results are consistent with our previous demonstration of preferential inhibition of the apoptosis-related kinases by MKP-1 and further support the contention that MKP-1, even in PIN, may shift the balance existing between cell proliferation and death. When expressed, it may inhibiting those pathways that lead to apoptosis.

Electronic Resource

1432-1920

Brain ; Post-mortem ; MRI ; Pathology

Springer Online Journal Archives 1860-2000

Medicine

Abstract We examined 21 brains from individuals more than 65 years of age by MRI and neuropathological methods to study the frequency and morphology of white matter changes. There were 16 brains from neurologically normal subjects (Group 1) while the remaining 5 (Group 2) had neurological disturbances. In Group 1 MRI showed high signal areas in the periventricular white matter in 12 brains and in the deep white matter in 9. All had focal areas, with confluent zones in 4; 3 cystic infarcts were also detected. Neuropathology in this Group showed periventricular changes of variable extent in all cases, vacuolated myelin around the perivascular spaces in 14 and degenerate myelin in 4. Macroscopic inspection showed 3 cystic lacunar infarcts, while areas of recent infarction were present on histology in 2. Four of the Group 2 brains had periventricular MRI changes; high signal areas in deep white matter were focal in 2 and confluent in 1. Cystic infarcts were detected in 3 cases. Neuropathology showed periventricular changes in all the brains; in 4 myelin around the perivascular spaces was vacuolated while degenerate myelin was demonstrated in 1. There were also old (1) and recent (2) lacunar infarcts. High signal areas in the white matter thus have different histological backgrounds but only in a minority of cases do they seem to be of pathological significance and, as a rule, they are not related to the presence of neurological disturbances. Correlative MRI-neuropathological studies are helpful for characterising abnormalities detected by techniques, like MRI, which are sensitive but not very specific.

Electronic Resource

1432-2307

Prostate ; Carcinoma ; Atypical adenomatous hyperplasia ; Prostatic intraepithelial neoplasia

Springer Online Journal Archives 1860-2000

Medicine

Abstract The term prostatic intraepithelial neoplasia (PIN) is an accepted diagnosis in pathology of the prostate. The diagnostic difference between atypical adenomatous hyperplasia (AAH) and adenosis is still under debate. A number of questions remain about the significance of grading of AAH and PIN, the biology of AAH and PIN as precursors of carcinoma, the possibility of treatment of AAH and PIN and whether AAH- and PIN-associated cancers differ from non-associated carcinoma. This paper reviews the results and discussions at the First International Consultation Meeting on Atypical Adenomatous Hyperplasia and Prostatic Intraepithelial Neoplasia and the Origins of the Prostatic Carcinomas. AAH is an architectural atypia of the prostate. The histological and cytological features of AAH are intermediate between BPH and low-grade carcinoma of the prostate. Cell kinetic findings show no distinct neoplastic pattern. AAH may be a precursor of transition zone carcinoma but the findings to date are inconclusive. Follow up studies should address whether the association of AAH and carcinoma is incidental or whether transition occurs between AAH and carcinoma. In contrast, PIN is an accepted preneoplastic lesion and the most likely precursor of the dorso-peripheral zone carcinoma. The diagnosis of high-grade PIN is clinically important, because high-grade PIN is associated with carcinoma in a high percentage of patients (38–100%). AAH- and PIN-associated cancers may not differ from other prostatic cancers. At present treatment for AAH and PIN without carcinoma is not indicated, but high-grade PIN warrants surveillance and follow up of the patient to identify a possible coexisting cancer. It must be stressed that AAH and PIN are multifocal lesions and both are age-associated.

Electronic Resource