Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas: an immunocytochemical study of 42 cases.

BACKGROUND: The natural history and growth mechanisms of cerebral cavernous angiomas are unclear, which makes them difficult to manage. We attempted to evaluate the evolutive potential of cavernomas by studying the proliferative capacity of cells. METHODS: We studied 42 histologically verified cavernomas with monoclonal antibody to proliferating cell nuclear antigen (PCNA), an accessory protein of the cell cycle, the rate of which is increased in proliferative cells. The PCNA Labeling Index (PCNA LI) was calculated in each case, and the results were compared with histologic findings (lacy areas, thick walls, thrombi, hemosiderin) and clinical features (epilepsy, hematomas, pseudotumorous signs). RESULTS: Thirty-six of 42 cases (85.7%) revealed stained cells. PCNA LI ranged from 1 to 48% (mean: 23.39%). Statistical analyses showed a positive correlation between PCNA LI and the extent of lacy areas (p < 0.05). On the contrary, collagenous-walled and thrombotic areas rarely showed positively stained cells. We found no relationship between PCNA LI and clinical features. CONCLUSIONS: A proliferative capacity of endothelial cells does exist in some areas of cavernomas and may explain, besides thromboses and hemhorrages, the growth and even de novo appearance of these lesions. Occurrence of fragile blood cavities, thickening of others, and changes in blood flow may influence the evolution of lesions. Our results suggest that in cavernomas, some areas may undergo specific changes, which makes them more dynamic lesions than previously thought.

Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q.

OBJECTIVES: To characterise clinically a large French family affected with cerebral cavernomas and to check for linkage of this condition to chromosome 7. METHODS: A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479. RESULTS: The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families--namely, a high clinical penetrance and the presence of multiple lesions within most of the affected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at 0=0.00) and D7S630 (Zmax=3.44 at 0=0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479. CONCLUSIONS: These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family.