Clinical Progression and Familial Occurrence of Cerebral Cavernous Angiomas
Clinical Progression and Familial Occurrence of Cerebral Cavernous Angiomas
Object: The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors.
Methods: Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor–β [TGFβ], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases).
The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFβ expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFβ, PDGF, and tenascin in more aggressive cavernomas.
Conclusions: The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.
Cavernous angiomas of the brain are common le sions occurring with a prevalence of approximately 0.5%. Their diagnosis has been drastically im proved by the widespread use of MR imaging. Familial forms with an autosomal-dominant transmission are ob served in 25 to 54% of cases.
Most cavernomas are indolent and stable lesions that are discovered incidentally or because of sporadic sei zures, and they remain unchanged on the follow-up studies obtained over the years. On the other hand, some cases show a more aggressive clinical behavior, which may lead to functional and even life-threatening risks. The main factors that can make a cavernoma an aggressive lesion inclu de hemorrhage (particularly extralesional and recurrent), enlargement of the cavernomatous matrix, de novo ap pearance, extensive calcifications, and familial occurrence.
Several studies have shown the expression of growth factors, mainly VEGF and TGFα, in brain cavernomas. It has been suggested as well that some potential regulatory effectors of angiogenesis, mainly VEGF, may play a role in the progressive and dynamic behavior of cavernomas.
In this study, we investigated the expression of some growth factors and proliferative indices, including VEGF, ten ascin, TGFβ, PDGF, Ki-67, and bcl-2 in a series of brain cavernomas. Our aim was to define whether the in do lent or progressive clinical behavior of both sporadic and familial forms is related to different expression of growth factors and proliferative indices in both caverno ma tissue and surrounding brain parenchyma.
Object: The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors.
Methods: Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor–β [TGFβ], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases).
The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFβ expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFβ, PDGF, and tenascin in more aggressive cavernomas.
Conclusions: The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.
Cavernous angiomas of the brain are common le sions occurring with a prevalence of approximately 0.5%. Their diagnosis has been drastically im proved by the widespread use of MR imaging. Familial forms with an autosomal-dominant transmission are ob served in 25 to 54% of cases.
Most cavernomas are indolent and stable lesions that are discovered incidentally or because of sporadic sei zures, and they remain unchanged on the follow-up studies obtained over the years. On the other hand, some cases show a more aggressive clinical behavior, which may lead to functional and even life-threatening risks. The main factors that can make a cavernoma an aggressive lesion inclu de hemorrhage (particularly extralesional and recurrent), enlargement of the cavernomatous matrix, de novo ap pearance, extensive calcifications, and familial occurrence.
Several studies have shown the expression of growth factors, mainly VEGF and TGFα, in brain cavernomas. It has been suggested as well that some potential regulatory effectors of angiogenesis, mainly VEGF, may play a role in the progressive and dynamic behavior of cavernomas.
In this study, we investigated the expression of some growth factors and proliferative indices, including VEGF, ten ascin, TGFβ, PDGF, Ki-67, and bcl-2 in a series of brain cavernomas. Our aim was to define whether the in do lent or progressive clinical behavior of both sporadic and familial forms is related to different expression of growth factors and proliferative indices in both caverno ma tissue and surrounding brain parenchyma.
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