Diagnostic Neuropathology (diagnostic + neuropathology)

Distribution by Scientific Domains

Selected Abstracts

Comparative study of commercially available anti-,-synuclein antibodies

E. Croisier
Immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis for Parkinson's disease, Dementia with Lewy bodies and Multiple System Atrophy (http://www.ICDNS.org). Nevertheless, no standardised protocol has been proposed. We have reviewed 242 of the 270 studies published until June 2005 that mentioned immunohistochemistry for anti-alpha synuclein on human tissue and we found that only 75 (31%) used commercial antibodies. We also noted that protocols, particularly dilution and antigen unmasking, varied between studies, even when the same antibody was employed. In order to establish a standardised protocol for alpha-synuclein immunohistochemistry, which can be applied in diagnostic neuropathology we tested seven commercial monoclonal antibodies in brains of subjects with Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, multiple sclerosis with incidental Lewy bodies and aged-matched normal brain and determined for each antibody the best suited protocol for antigen unmasking. We evaluated the intensity of immunolabelling in Lewy bodies, neuropil threads, dendrites, pre-synaptic terminals, granular cytoplasmic positivity, peri-axonal positivity, glial inclusions and non-specific immunolabelling. Although our results showed that all the antibodies detected alpha-synuclein inclusions, differences were noted between antibodies, particularly with regard to the detection of glial inclusions. From our study, the best antibodies of the seven tested appeared to be those directed against amino acids 116,131 and 15,123 and we suggest them to be used in routine diagnostic practice for alpha-synucleinopathies. [source]

Immunohistochemical estimation of cell cycle entry and phase distribution in astrocytomas: applications in diagnostic neuropathology

Ian S. Scott
An immunohistochemical method for assessing cell cycle phase distribution in neurosurgical biopsies would enable such data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in glial neoplasms, without the requirement for flow cytometric analysis. Paraffin-embedded sections of intracerebral gliomas (n = 48), consisting of diffuse astrocytoma (n = 9), anaplastic astrocytoma (n = 8) and glioblastoma (n = 31), were analysed by immunohistochemistry using markers of cell cycle entry, Mcm-2 and Ki67, and putative markers of cell cycle phase, cyclins D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis). Double labelling confocal microscopy confirmed that the phase markers were infrequently coexpressed. Cell cycle estimations by immunohistochemistry were corroborated by flow cytometric analysis. There was a significant increase in Mcm-2 (P < 0.0001), Ki67 (P < 0.0001), cyclin A (P < 0.0001) and cyclin B1 (P = 0.002) expression with increasing grade from diffuse astrocytoma through anaplastic astrocytoma to glioblastoma, suggesting that any of these four markers has potential as a marker of tumour grade. In a subset of glioblastomas (n = 16) for which accurate clinical follow-up data were available, there was a suggestion that the cyclin A:Mcm-2 labelling fraction might predict a relatively favourable response to radical radiotherapy. These provisional findings, however, require confirmation by a larger study. We conclude that it is feasible to obtain detailed cell cycle data by immunohistochemical analysis of tissue biopsies. Such information may facilitate tumour grading and may enable information of prognostic value to be obtained in the routine diagnostic laboratory. [source]

Ballooned neurones in the limbic lobe are associated with Alzheimer type pathology and lack diagnostic specificity

Y. Fujino
Ballooned neurones (BNs) are one of the pathological hallmarks of several neurodegenerative diseases, including Pick's disease, corticobasal degeneration and argyrophilic grain disease (AGD). They have also been described in Alzheimer disease (AD), but the frequency of BNs in AD has not been systematically addressed. In the present study, immunohistochemistry for ,B-crystallin was used as a sensitive method to detect BNs to determine the frequency of BNs in the limbic lobe in AD. At least a few BNs were detected in the limbic lobe of virtually all AD cases, and their density correlated with Braak stage, as well as the density of neurofibrillary tangles and senile plaques in the limbic lobe. The density of BN tended to be greater in AD cases with concurrent AGD than in pure AD. Given the high prevalence of AD in brain banks for neurodegenerative disease and the frequent presence of BNs in these areas with ,B-crystallin immunohistochemistry, the present findings further indicate that BNs confined to the limbic lobe lack specificity in diagnostic neuropathology. [source]

The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma

CANCER, Issue 7 2002
A Surveillance, End Results analysis, Epidemiology
Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL appears to be increasing. METHODS PCNSL incidence data from 1973,1997 were obtained from the nine Surveillance, Epidemiology and End Results (SEER) registries. To limit the influence of the human immunodeficiency virus on incidence rates, data of never,married males and females and persons of unknown marital status were excluded. As a surrogate for new technology, SEER data were reviewed by dates of diagnosis (surrogate for imaging) and compared with glioma incidence (surrogate for stereotactic neurosurgery and improved diagnostic neuropathology). Age-adjusted incidence rates were estimated and compared for the period prior to computed tomography (CT) (1973,1984) and the magnetic resonance imaging (MRI) period (1985,1997). The estimated annual percent change was calculated based on linear regression analyses using SEER*STAT. RESULTS The incidence of PCNSL appears to be increasing in all SEER registries examined. All age groups demonstrated an increase over time. This increase was observed both in the CT era as well as in the MRI era. PCNSL age-adjusted incidence (0.15 to 0.48, a 3-fold increase) outpaced that of systemic lymphoma (14.1 to 18.5, a 33% increase) for the same registries over the same time periods. The rate of increase has begun to slow since 1985; the estimated annual percent change for PCNSL was three-fold higher during the period 1973,1985 compared with 1986,1997. CONCLUSION The incidence rate of PCNSL continues to rise. The increase is evident in all age groups and in both genders. Data from the current study suggest that improved diagnostic tools, such as CT or MRI, cannot explain this increase. Cancer 2002;95:1504,10. 2002 American Cancer Society. DOI 10.1002/cncr.10851 [source]