Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study.

BACKGROUND: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. METHODS: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98). RESULTS: Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048). CONCLUSION: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

Perisynaptic aggrecan-based extracellular matrix coats in the human lateral geniculate body devoid of perineuronal nets.

The extracellular matrix surrounds different neuronal compartments in the mature nervous system. In a variety of vertebrates, most brain regions are loaded with a distinct type of extracellular matrix around the somatodendritic part of neurons, termed perineuronal nets. The present study reports that chondrotin sulfate proteoglycan-based matrix is structured differently in the human lateral geniculate body. Using various chondrotin sulfate proteoglycan-based extracellular matrix antibodies, we show that perisomatic matrix labeling is rather weak or absent, whereas dendrites are contacted by axonal coats appearing as small, oval structures. Confocal laser scanning microscopy and electron microscopy demonstrated that these typical structures are associated with synaptic loci on dendrites. Using multiple labelings, we show that different chondrotin sulfate proteoglycan components of the extracellular matrix do not associate exclusively with neuronal structures but possibly associate with glial structures as well. Finally, we confirm and extend previous findings in primates that intensity differences of various extracellular matrix markers between magno- and parvocellular layers reflect functional segregation between these layers in the human lateral geniculate body.

Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex.

The ectoenzyme tissue non-specific alkaline phosphatase (TNAP) is mostly known for its role in bone mineralization. However, in the severe form of hypophosphatasia, TNAP deficiency also results in epileptic seizures, suggesting a role of this enzyme in brain functions. Accordingly, TNAP activity was shown in the neuropil of the cerebral cortex in diverse mammalian species. However in spite of its clinical significance, the neuronal localization of TNAP has not been investigated in the human brain. By using enzyme histochemistry, we found an unprecedented pattern of TNAP activity appearing as an uninterrupted layer across diverse occipital-, frontal- and temporal lobe areas of the human cerebral cortex. This marked TNAP-active band was localized infragranulary in layer 5 as defined by quantitative comparisons on parallel sections stained by various techniques to reveal the laminar pattern. On the contrary, TNAP activity was localized in layer 4 of the primary visual and somatosensory cortices, which is consistent with earlier observations on other species. This result suggests that the expression of TNAP in the thalamo-recipient granular layer is an evolutionary conserved feature of the sensory cortex. The observations of the present study also suggest that diverse neurocognitive functions share a common cerebral cortical mechanism depending on TNAP activity in layer 5. In summary, the present data point on the distinctive role of layer 5 in cortical computation and neurological disorders caused by TNAP dysfunctions in the human brain.

Donor face reconstruction in a case of facial allotransplantation: technical note.

Families of organ donors are much more reluctant to approve donation of the corneas, face, and hands than of internal organs. The idea to "sacrifice" the face of a dead loved one is shocking to many. Moreover, most national laws, including Belgian laws, demand respect for the corpse. When mourners view an open coffin, visible parts such as the hands and face should appear normal. Hence, careful donor face reconstruction is required in a case of facial allotransplantation. We present a technique for donor face reconstruction that is both expedient and cost-effective. Instead of laboratory-cured silicone or acrylic polymers with internal and external coloration, an A-silicone impression material with a 2-minute set time and external colouring is used.

[Papillary renal cell carcinoma]. / Papillaris vesesejtes veserák.

The authors present a case of a papillary type renal cell carcinoma. The tumor is mostly discovered accidentally; a histopathological evaluation is indispensable for an exact diagnosis. Because of a better prognosis, differentiation of this tumor type from the classic variant of renal cell carcinoma is necessary, however, the contralateral appearance of a second tumor is not to be excluded, which necessitates a strict patient follow-up. Prevalence of this tumor is higher in patients with chronic dialysis.

Development of atherosclerosis and plaque biology.

Atherosclerosis is a leading issue in mortality and morbidity in the civilized world. A number of hypotheses for atherogenesis indicate the complexity of initiation and development of this multifactorial disease. Morphologic types of lesions have long since been studied in order to understand plaque evolution and determinants of plaque complication, a frequent cause of acute ischemic accidents. Chemical and pathophysiological studies defined the wide spectrum of molecular interactions between cellular elements of atherosclerotic lesions. Recently, molecular biologic investigations provide a deeper insight into genetic predispositions for the disease and have widened our understanding of the pathogenic mechanisms. Until we can diminish the high prevalence of the disease, precise information is needed on the evolution of atherosclerosis in order to slow progression, select optimal therapies and prevent plaque complications and their consequences.

World Health organization (WHO) and the World Heart Federation (WHF) pathobiological determinants of atherosclerosis in youth study (WHO/WHF PBDAY Study) 1986-1996. Histomorphometry and histochemistry of atherosclerotic lesions in coronary arteries and the aorta in a young population.

BACKGROUND AND AIM: The present work is a chapter in an investigation directed by the World Health Organization on the Pathobiological Determinants of Atherosclerosis In Youth (WHO-PBDAY). Our aim was to study the development of atherosclerotic lesions in a young population. METHODS AND RESULTS: Samples of left anterior descending coronary artery (LDC) and thoracic (TA) and abdominal aorta (AA) from five Collaborating Centres (Budapest/Hungary, Havana/Cuba, Heidelberg/Germany, Mexico City/Mexico, Peradeniya/Sri Lanka) of 214 subjects who died aged 15 and 34 were analysed at the Budapest Reference Centre. Slides stained with haematoxylin-eosin and with stains for extracellular matrix were quantitatively and qualitatively evaluated. Mean intima/media (I/M) ratio and the prevalence of type III-IV lesions (preatheroma; atheroma; calcified and fibrous atheroma) were determined and compared in different risk factor (high blood pressure, smoking) groups. High I/M ratio was found in the LDC and type III-IV lesions were frequently found both in the LDC and in the AA. I/M ratio and the occurrence of type III-IV lesions increased in all arteries by age. Atherosclerotic lesions in men were more severe, particularly in the LDC. Geographic origin had a limited effect on the histologic lesion parameters. Appearance of type III-IV lesions was associated with substantially different extracellular matrix changes. Myoelastic layer formation was found in each artery in both early and type III-IV lesions. Hypertension was associated with higher prevalence of type III-IV lesions in all arteries, in particular, in the TA; smoking showed a significant effect on the AA only. CONCLUSIONS: Atherosclerotic lesions were found in many of these young subjects. The effect of hypertension and smoking on their development suggests that control of risk factors, beginning in early adolescence, could help to prevent cardiovascular diseases.