Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).

BACKGROUND: Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. OBJECTIVES: We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. METHODS: IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. RESULTS: The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. CONCLUSIONS: This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.

Exploration of hemispheric specialization and lexico-semantic processing in unilateral temporal lobe epilepsy with verbal fluency tasks.

Verbal production has been shown to rely on both hemispheres differentially. To determine how lateralized brain lesions affect the generation of isolated words, we evaluated three subject groups: normal controls (n=22), and patients with right (n=23), and left (n=22) non-operated temporal lobe epilepsy (TLE) using three verbal fluency tasks (letter, phonetic, semantic). LTLE patients produced fewer words than controls in the phonetic, letter, semantic conditions, whereas RTLE patients were only impaired in the semantic task. Hence, there would be a hemispheric specialization in language where phonetic processing involves mostly the left temporal lobe and semantic aspects of production involve both temporal lobes. And, in order to study disruption of semantic lexicon involved in supermarket fluency (to name things which can be bought in a supermarket), specific indicators Tröster et al., (1998) [Tröster AI, Fields JA, Testa JA, Paul RH, Blanco CR, Hames KA, Salmon DP, Beatty WW. Cortical and subcortical influences on clustering and switching in the performance of verbal fluency Tasks, Neuropsychologia 1998;36:295-304.] were exploited. Our results indicated that TLE groups made fewer category shifts than controls. Also, RTLE patients used labels more frequently and produced fewer exemplars. Results show the specificity of processing according to cue, and suggest that the semantic fluency deficits due to TLE be primarily due to an alteration of the mental lexicon.

Age effect in recall performance according to the levels of processing, elaboration, and retrieval cues.

The present study was conducted to investigate the incidence of several factors contributing to age-related memory decrement. Variables manipulated include quality (level of processing encoding conditions), the degree of effort and encoding quantitative elaboration (active/passive encoding conditions), and the influence of retrieval support (free-/cued recall conditions). In support of the environmental support hypothesis, middle-old and old subjects benefited more than young ones from cued recall in all the memory tests. Moreover, the results showed a differential (qualitative vs. quantitative) impairment of conceptual processing between the middle-old and the old-age groups. In the middle-olds, age differences were abolished by deep processing in old adults, age differences were attentuated only with deep and active processing associated with retrieval support. These gradual memory impairments are evaluated according to Mandler's model of memory (1979, In L. G. Nilsson [Ed.], Perspective in memory research. Hillsdale: Lawrence-Erlbaum), and the environmental support hypothesis is discussed in terms of the involvement of encoding and retrieval operations required by the memory task.

Correlations between granule cell dispersion, mossy fiber sprouting, and hippocampal cell loss in temporal lobe epilepsy.

PURPOSE: Correlations between granule cell dispersion (GCD), collateral mossy fiber (MF) sprouting, and hippocampal cell loss were studied to assess the relation between GCD and synaptic reorganization in the dentate gyrus of patients with epilepsy. METHODS: Twenty specimens from patients with medically intractable temporal lobe epilepsy (TLE) were studied along with two control specimens. GCD was considered to be present when the stratum granulosum was wider than 120 microm, the close apposition between the granule cell (GC) soma was lost, and GCs were scattered in the molecular layer (ML). Patterns of MF sprouting were differentiated as wide or narrow according to the area of neo-Timm's staining in the ML. GC loss and volumetric cell-density decreases in the different subfields were assessed. RESULTS: MF sprouting was observed in 16 (80%) and GCD in nine (45%) cases. A significant correlation was found between MF sprouting and cell loss in all the subfields except the cornu Ammonis field 2 (CA2). A wide band of MF sprouting was associated with severe cell loss. Cases with GCD had a wide band of MF sprouting and also a higher degree of cell loss than cases without GCD. CONCLUSION: GCD is associated with a specific pattern of MF sprouting, but cell loss was found to be a major determinant for MF reorganization.

Bilateral decrease in interictal hippocampal blood flow in unilateral mesiotemporal epilepsy.

OBJECT: The goal of this study was to determine whether regional cerebral blood flow (rCBF) changes that were found contralaterally to a verified unilateral epileptic focus were associated with the spatiotemporal organization of epileptic abnormalities. METHODS: The CBF in both hippocampi was assessed using stable Xe-enhanced computerized tomography in a series of 19 patients with unilateral mesiotemporal epilepsy. Results were compared according to the distribution of interictal spiking and the spatiotemporal organization of the ictal discharges as determined by stereoelectroencephalography. Two groups were defined: in Group 1 (nine patients), the discharge remained unilateral; in Group 2 (10 patients), the discharge spread to contralateral mesiotemporal structures. For Group 1, the rates of ipsi- and contralateral hippocampal blood flow (HBF) were 32.88+/-15.53 and 45.88+/-17.19 ml/100 g/minute, respectively, whereas in Group 2 they were 36.7+/-11.54 and 36.4+/-11.27 ml/100 g/minute (mean+/-standard deviation). A two-way analysis of variance combining type of seizure (Group 1 compared with Group 2) and HBF (ipsi- compared with contralateral absolute values) demonstrated a main effect for HBF (F[1,17] = 5.051; p = 0.0382), a significant interaction between the two factors (F[1,17] = 6.188; p = 0.0235), and no main effect for type of seizure (F[1,17] = 0.258; p = 0.6178). CONCLUSIONS: In unilateral mesiotemporal epilepsy, asymmetrical interictal hippocampal perfusion was correlated with restricted unilateral ictal discharges, whereas bilateral hippocampal hypoperfusion was correlated with ictal discharges spreading to the contralateral mesiotemporal structures. The lack of correlation between the degree of hypoperfusion and the percentage of neuron cell loss indicated that the decrease in rCBF has both functional and lesional origins.