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A histologic and immunocytochemical study of choroid plexus tumors of the dog.

Sixteen choroid plexus (CP) tumors in 12 male and four female adult dogs were analyzed microscopically. Tumors were in the lateral (six), third (six), and fourth (four) ventricles. The average age of the dogs was 6 years. Tumors were classified by the following criteria: 1) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma (CPP), which resembled normal choroid plexus and had low mitotic activity; 2) choroid plexus papilloma with atypical features (atypical CPP), which had increased cellular density, nuclear atypia, two to four mitoses per 40x microscopic field, necrosis, and infiltration of the brain parenchyma and/or leptomeninges; and 3) choroid plexus carcinoma (CPC), which had marked nuclear atypia, poorly formed papillae, greater than four mitoses per 40x microscopic field, abnormal mitotic figures, and/or extraneural metastasis. The 16 tumors were classified either as CPP or atypical CPP (none as CPC). Statistically significant associations between brain infiltration and necrosis and atypical CPP were identified. Immunohistochemical studies in 11 tumors demonstrated staining for keratin in three tumors, two of which also reacted with carcinoembryonic antigen (CEA). There was no immunoreactivity with glial fibrillary acidic protein or epithelial membrane antigen. Choroid plexus from one of three control dogs stained focally for cytokeratin only. It is concluded that normal choroid plexus and CP tumors in the dog express epithelial, but not glial differentiation.

Animals↗

Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain.

T4 is bound to transthyretin (TTR; 75%) and albumin (Alb; 25%) in rat serum and only to TTR in cerebrospinal fluid (CSF). In addition to the liver, TTR is synthesized in large amounts in the choroid plexus and then secreted into the CSF, suggesting that serum T4 could be transported to the CSF and brain via the choroid plexus. We determined whether serum T4 bound to TTR is transported into the choroid plexus and CSF. N-Bromoacetyl-L-[125I]T4, a derivative of T4 that binds covalently to TTR, was used as the affinity label for the T4-binding site on TTR. Rats were injected with [125I]T4, acetyl-[125I]T4 covalently bound to human TTR ([125I]T4Ac.human hTTR), or acetyl-[125I]T4 covalently bound to human Alb ([125I]T4Ac.hAlb). The quantities of [125I]T4Ac.hTTR and [125I]T4Ac.hAlb present in the choroid plexus, CSF, and brain 90 min later were barely detectable. In contrast, [125I]T4 injected as the unbound form accumulated in the choroid plexus and CSF to levels 6-11 times higher than with [125I]T4Ac.hTTR (P less than 0.005). We then used a synthetic flavonoid (EMD) that competitively inhibits binding of T4 to serum TTR and transiently increases serum free T4 to determine the role of choroid plexus TTR and CSF TTR in the transport of T4 from serum to brain. Rats were given 110 microCi [125I]T4 15 min after the injection of vehicle, a low (0.3 mumol/100 g BW) or high dose of EMD (2.0 mumol/100 g BW). Rats were killed 60 min later. In serum, the percentage of [125I]T4 bound to TTR decreased and free T4 increased similarly in the low and high dose EMD-treated rats. In contrast, the percentage of [125I]T4 bound to TTR in choroid plexus and, subsequently, CSF was significantly decreased in rats given the high dose of EMD, but was not affected by the low dose of EMD, suggesting that in high doses, EMD crossed from serum to choroid plexus and CSF and occupied TTR-binding sites for T4. There was a significant decrease (P less than 0.05) in the percentage of injected [125I]T4 in the high dose vs. the low dose EMD-treated rats in total choroid plexus (61%), 1 ml CSF (94%), and 1 g cerebral cortex (46%) and cerebellum (46%).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Expression and regulation of vascular endothelial growth factor in choroidal fibroblasts.

Subretinal neovascularization is a severe sight-threatening complication into age-related macular degeneration. Previous immunohistochemical studies on surgically removed neovascular membranes have revealed that these membranes, in addition to the neovascular stroma, are comprised of several different cell types such as retinal pigment epithelial (RPE) cells, choroidal fibroblasts and vascular endothelial cells. Since vascular endothelial growth factor (VEGF) potently and specifically induces angiogenesis it was investigated whether VEGF is expressed and/or inducible in choroidal fibroblasts and RPE cells. Choroidal fibroblasts and RPE cells were isolated from human adult post-mortem eyes and expression of VEGF mRNA and protein was measured. By using Northern blotting, both choroidal fibroblasts and RPE cells were found to express VEGF mRNA at low levels. In order to examine whether this VEGF expression was further inducible, the intracellular effector enzyme protein kinase C was activated by phorbol esters. This activation resulted in a prominent increase in VEGF mRNA in choroidal fibroblasts, but not in RPE cells, with a maximal increase detected after 6 h. Elevation of intracellular cyclic AMP levels by forskolin had no clear effect on VEGF mRNA in either cell type. Stimulation with interleukin-1, transforming growth factor beta, tumour necrosis factor alpha and platelet derived growth factor was tested to see if VEGF expression is cytokine inducible. Both interleukin-1 and transforming growth factor beta induced VEGF expression in choroidal fibroblasts although with different time courses. Whereas the transforming growth factor beta effect was transient the interleukin-1 effect was sustained for at least 48 h. None of the cytokines tested affected VEGF expression in RPE cells. By using Western blotting, it was further found that stimulation with interleukin-1 induced VEGF protein expression in choroidal fibroblasts but not in RPE cells. In conclusion, choroidal fibroblasts respond by elevated VEGF mRNA levels after phorbol ester, interleukin-1 and transforming growth factor beta stimulation and elevated VEGF protein levels after phorbol ester and interleukin-1 stimulation suggesting that choroidal fibroblasts may be target cells for increased VEGF synthesis secondary to paracrine cytokine production.

Aged↗

[A comparative study of choroidal innervation in the human and the rabbit (oryctolagus cuniculus)].

OBJECTIVE: To analyze morphological differences between the choroidal innervation of the human and the rabbit, the latter being a species frequently used as an experimental model of human ocular diseases. METHODS: Twelve human and 12 rabbit choroidal whole mounts were processed using an indirect immunohistochemical technique, peroxidase-anti-peroxidase and antibodies against 200 kD neurofilament. RESULTS: Choroidal nerve fibers were perivascular and intervascular. Perivascular fibers surrounded all arteries forming a network that was more developed in the rabbit. In humans, intervascular fibers were mainly concentrated at the posterior pole where they formed a denser and more highly organized plexus than in the rabbit, which did not exhibit a preferential location for these fibers. Human choroidal ganglion cells were far more numerous than in the rabbit and were concentrated in a circumferential area corresponding to the entrance of the short posterior ciliary arteries of the submacular area. In the rabbit, these cells were restricted to the peripheral choroid. CONCLUSIONS: Some differences were observed between human and rabbit choroidal innervation. The abundance of ganglion cells and their preferential distribution could be necessary to maintain a constant blood flow in the central area of the human choroid. The lack of organization of rabbit choroidal innervation at the posterior pole could be associated with an absence of the macula. These differences, along with peculiarities of retinal vascularization, should be taken into consideration when using the rabbit as an experimental model to study human eye diseases in which regulation of choroidal blood flow is involved.

Animals↗

Karyotyping of fetuses with isolated choroid plexus cysts is not justified in an unselected population.

OBJECTIVE: The main objective of this study was to determine whether isolated choroid plexus cysts are a risk factor for trisomy 18. METHODS: A total of 12,672 unselected patients were examined, and the outcome of fetuses with choroid plexus cysts was assessed. The cases with choroid plexus cysts were selected from the 12,672 patients and further divided into cases with minor markers of aneuploidy and cases with associated structural anomalies. Previous similar work was reviewed, analyzed, and, where possible, compared with the results of this study. RESULTS: The findings revealed 366 fetuses with choroid plexus cysts (2.9%). Thirty-three percent of fetuses with trisomy 18 had choroid plexus cysts, and, in every case, structural anomalies were also present. From the 12 cases with choroid plexus cysts in addition to major associated anomalies, amniocentesis revealed 2 cases of trisomy 18. Forty-three patients who had choroid plexus cysts and minor anomalies within our population had normal outcomes. CONCLUSIONS: These results indicate that the risk of amniocentesis is not acceptable if isolated choroid plexus cysts are isolated findings. More data are needed to establish whether choroid plexus cysts and other soft signs independently increase the risk of aneuploidy.

Adolescent↗

Immunocytochemical detection of insulin-like growth factor II (IGF-II) in choroid plexus papilloma: a possible marker for differential diagnosis.

BACKGROUND: Insulin-like growth factor II (IGF-II) has been detected in the choroid plexus of animals by means of immunohistochemistry and in situ hybridization, and this factor is thought to play an important role in the central nervous system (CNS). Little is known, however, about the presence and localization of this substance in the choroid plexus and in choroid plexus papilloma in humans. MATERIALS AND METHODS: 5 normal choroid plexus and 10 choroid plexus papillomas were examined for IGF-II by immunocytochemistry. IGF-II was not detected in normal human choroid plexus, whereas it was found in choroid plexus papilloma. Furthermore, to assess the possibility that IGF-II could serve as an immunohistological marker of choroid plexus papilloma, we used the same technique to examine paraffin-embedded samples from various kinds of brain tumors. RESULTS AND CONCLUSION: Our results suggest that IGF-II may be a useful marker for choroid plexus papilloma in differential diagnosis.

Adolescent↗

Transepithelial transport of organic anions across the choroid plexus: possible involvement of organic anion transporter and multidrug resistance-associated protein.

Transport characteristics of 17beta-estradiol 17beta-D-glucuronide (E217betaG), a dual substrate of the transporters for cellular uptake (organic anion-transporting polypeptide 1 or oatp1) and cellular excretion (multidrug resistance-associated protein 1or MRP1), in the rat choroid plexus were studied in vivo and in vitro. The uptake of E217betaG into isolated choroid plexus was mediated by an energy-dependent system with a Km of 3.4 microM. Together with the previous finding that oatp1 is localized on the apical membrane of choroid plexus, these results suggest that oatp1 is responsible for the uptake of this ligand. After intracerebroventricular administration, elimination of E217betaG from cerebrospinal fluid was probenecid sensitive and much more rapid than that of inulin; less than 2% of the administered E217betaG and 40 to 50% of inulin remained in the cerebrospinal fluid 20 min after intracerebroventricular administration. In addition, the amount of E217betaG associated with choroid plexus at 20 min was negligible, suggesting the presence of an efficient excretion system on the basolateral membrane of choroid plexus. Expression of MRP1 was detected in choroid plexus. Semiquantitative reverse transcription-polymerase chain reaction and Western blot analyses indicated that the expression level of MRP1 in choroid plexus is about four or five times higher than that in the lung, one of the tissues exhibiting high expression of MRP1. Together with the in vivo vectorial transport of E217betaG, these results can be accounted for by assuming that there is basolateral localization of MRP1 in choroid plexus. Combined, oatp1 and MRP1 may synergistically mediate the efficient transcellular transport of E217betaG across choroid plexus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Optic nerve and peripapillary choroidal microvasculature of the rat eye.

PURPOSE: To investigate the three-dimensional microvascular anatomy of the optic nerve and peripapillary choroid in the rat eye. METHODS: Gross vascular anatomy of the posterior eye segment of Wistar rats was studied in serial microsections with a light microscope. The optic nerve and peripapillary choroidal vessels were sequentially microdissected, using methylmethacrylate corrosion microvascular castings, and were examined with a scanning electron microscope to determine the three-dimensional relationships of the vessels. RESULTS: The posterior ciliary artery traveled along the inferior side of the optic nerve sheath, directly entered the optic nerve head, and divided into three branches: the central retinal artery and medial and lateral long posterior ciliary arteries, which provided several short branches to the choroid. The optic nerve head vasculature was consistently nourished by a recurrent arteriole from the central retinal artery and an arteriole from the choroidal artery at the peripapillary choroid. The central retinal vein flowed into a venous anastomosis along the optic disc border of the peripapillary choroid. Capillaries within the optic nerve drained into the central retinal vein, the marginal venous anastomosis of the peripapillary choroid, and the pial veins, all of which flowed into the posterior ciliary veins along the optic nerve sheath. CONCLUSIONS: The findings illustrate vascular anatomic differences in optic nerve and peripapillary choroidal microcirculation between rat and human. In rats, the peripapillary choroid plays a significant role in both blood supply and venous drainage of the optic nerve head. The central retinal artery also contributes to the optic nerve head circulation.

Animals↗

[Idiopathic sclero-choroid calcification].

BACKGROUND: Idiopathic sclerochoroidal calcification (ISC) is an unusual, benign disorder occurring at the level of the posterior choroidea and sclera. Clinical differential diagnosis includes choroidal osteoma, choroidal metastasis, choroidal melanoma, choroidal amelanotic naevus and choroiditis. PATIENT: A 61-year old man was referred with the diagnosis of multifocal choroidal tumor in both eyes. Fundoscopy showed bilateral yellow lesions located near the superotemporal arcade. RESULTS: Fluorescein angiography shows the late staining of the choroidal lesions. Ultrasonographically highly reflective lesions (sclerochoroidal placoid lesions at the sclero-choroidal interface in the CT) confirms the clinical diagnosis. The serum calcium and phosphate metabolism is normal. CONCLUSION: The Idiopathic Sclerochoroidal Calcification (ISC) is a rare echographical differential diagnosis to the choroidal osteoma. ISC is a heterotopic calcification of the posterior pole in both eyes, usually located near the superotemporal arcade.

Calcinosis↗

Hindlimb-suspension and spaceflight both alter cGMP levels in rat choroid plexus.

Effects of actual and simulated weightlessness on choroidal guanylate cyclase activity were evaluated by assaying the production of cyclic guanosine monophosphate (cGMP), a second messenger involved in mechanisms regulating the secretion of cerebrospinal fluid (CSF) in choroid plexus. Cyclic cGMP was measured, using radio-immunoassay, in choroidal extracts of hindlimb-suspended rats (HLS rats), adapted to an anti-orthostatic restraint for 30 min., or for 3, 9 or 14 days and after a 17-day spaceflight (Life and Microgravity SpaceLab experiment; LMS). Basal cGMP levels were slightly but significantly decreased in the first 30 min. of the HLS experiment, whereas they were significantly increased in rats adapted to longer anti-orthostatic restraints. LMS flight rats demonstrated a similar increase in the choroidal cGMP baseline. After natriuretic peptide stimulation, i.e. using ANP (atrial natriuretic peptide) or BNP (brain natriuretic peptide), choroidal cGMP contents were typically increased (by 1.5-2 times; p<0.05) in control rats (LMS and HLS experiments), but not significantly elevated in suspended rats, except for those adapted to HLS for 14 days. In these animals the ANP-dependent cGMP production was significantly increased (by about 3 times; p<0.005). The ANP- or BNP-dependent responses were similarly abolished in LMS flight rats, which were dissected 4-6 hours after return to Earth's gravity. The role of corticosteroids was also investigated during the LMS experiment. Results on choroidal functions revealed a lack of significant change of cGMP levels between adrenalectomized and sham-operated rats. For the first time, it is reported that both basal and ANP- stimulated cGMP levels are dramatically changed over the first 14 days of suspension, i.e. with experiments known to simulate some effects of weightlessness. Basal choroidal cGMP levels are also increased after 17 days in space, suggesting that space adaptation also impacts choroidal guanylate cyclase activities. However, the absence of ANP-dependent cGMP increase, observed in LMS flight animals, suggests that HLS could not simulate all the spaceflight effects. Thus, these preliminary results seem to show that a natriuretic peptides-independent s stem is involved in choroidal adaptation to spaceflight.

Adaptation, Physiological↗

Oral fluorescein angiography in patients with choroidal neovascularization and macular degeneration.

OBJECTIVE: To evaluate image quality of oral fluorescein angiography in patients with age-related macular degeneration and choroidal neovascularization. MATERIALS AND METHODS: Twenty four patients with proven choroidal neovascularization were examined in a prospective observational case series. Confocal oral and intravenous fluorescein angiography were performed using the Heidelberg Retina Angiograph. Oral and intravenous image quality were compared in a masked fashion. RESULTS: Choroidal neovascularization could be diagnosed in all patients using intravenous angiograms. Oral fluorescein angiography accurately detected the presence or absence of choroidal neovascularization in all patients and could determine the classification of choroidal neovascularization, location, and extent and borders in 20 (83.3%) of 24 patients. Early, mid, and late phases of oral angiograms occurred at 8, 15, and 26 minutes, respectively. CONCLUSION: Oral fluorescein angiography using the confocal Heidelberg Retina Angiograph allowed detection of choroidal neovascularization in all patients in this study. Visualization of extent and type of choroidal neovascularization was possible in most eyes with choroidal neovascularization. These findings suggest oral angiography is an excellent screening tool for choroidal neovascularization and allows guidance of treatment in the majority of cases.

Administration, Oral↗

[Ultrastructure study on the RPE, Bruch's membrane and choroid after laser photocoagulation of the retina].

OBJECTIVE: To observe ultrastructural changes and repair process of retina after laser photocoagulation of the retina, in order to provide histopathologic findings of laser treatment for RPE and choroidal diseases. METHODS: In seven patients with orbital malignant tumor needed exenteration, the normal retina was coagulated (using I, II, or III grade photic spot) 1, 3, or 7 days before the exenteration after signing consent by the patients. The retina and the choroid from these enucleated eyeballs were observed by electron microscope. RESULTS: One day after photocoagulation (I grade photic spot), some RPE cells were swollen and necrotic, with partial disappearance of microvilli. The number or RPE was reduced. Bruch's membrane was intact. Endothelial cells of choroidal capillaries were swelled with occlusion in a few of the lumens. In III grade photic spot, many RPE cells were lysed. Vacuoles were found in Bruch's membrane. Many choroid capillaries were occluded. In III grade photic spot, numerous RPE cells were disappeared and Bruch's membrane was destroyed partially. Middle size vessels in the choroid were damaged. Three days after photocoagulation, edema of RPE cells and choroid was relieved. Phagocytes appeared in the damaged area RPE cells and fibrous tissue in choroid started to proliferate. Seven days after photocoagulation, damage area was covered by proliferative RPE. Choroid vessels were decreased in number and fibrosis was appeared in the stroma. CONCLUSIONS: Photocoagulation causes edema and necrosis of RPE and various degrees destruction of Bruch's membrane and choroidallvessels. Subsequently, the damaged area is covered by proliferative RPE cells and fibrous tissue. Diseases of the RPE and choroid can be treated by laser at various degrees of energy.

Bruch Membrane↗

[Indocyanine green videoangiography of the choroidal circulation in the experimental retinal opacity induced by blunt trauma].

Retinal opacity was experimentally induced by blunt trauma to the rabbit eye and the damage to the choroidal circulation was investigated immediately thereafter by using indocyanine green (ICG) videoangiography. Ten pigmented rabbit eyes were used. In the early phase, the defect of choroidal inflow (10 eyes), the twitch of the choroidal artery (2 eyes) and the reflux of the vortex vein (5 eyes) could be observed dynamically. The defect of choroidal inflow showed its peak around the point where the choroidal arteries branched off from ciliary arteries and disappeared within a few second to over ten seconds. The reflux from the vortex vein seemed to be important as collateral pathway. In the middle phase, several points of ICG leakage were observed around the apex of the delayed area of choroidal circulation (9 eyes). This ICG leakage was intra-choroidal and seemed to be caused by the breakdown of the great vessels at the outer layer of the choroid. This study indicates that ICG videoangiography could observe various choroidal circulatory disturbances following blunt trauma and may be useful in delineating the pathogenesis of retinal opacity.

Animals↗

[Choroidal vascular lesions in serous retinal detachment viewed with indocyanine green angiography].

In serous retinal detachment due to damaged retinal pigment epithelium (RPE), fluorescein angiography shows dye leakage into the subretinal space from the choroid. We performed indocyanine green (ICG) angiography in 110 eyes with serous retinal detachment comprising 71 eyes with central serous chorioretinopathy (CSC), 19 with bullous retinal detachment, 18 with Harada's disease, and 2 with toxemia of pregnancy. Choroidal tissue staining was present around the site of subretinal leakage in late-phase ICG angiograms from 63 eyes with CSC and 18 with bullous retinal detachment. ICG angiography also showed leakage from choroidal vessels in 16 eyes with Harada's disease and 2 with toxemia of pregnancy. As a common feature, ICG angiography showed choroidal vascular hyperpermeability in various types of serous retinal detachment. Choroidal circulation was delayed in Harada's disease and toxemia of pregnancy. Choroidal hypoperfusion and hyperpermeability of choroidal vessels probably contribute to the damage of RPE, and choroidal vascular hyperpermeability probably provides fluid pressure to move fluid into the subretinal space from the choroid.

Adult↗

Innervation of orbital and choroidal blood vessels by the pterygopalatine ganglion in pigeons.

Orbital and choroidal blood vessels in mammals are known to receive a parasympathetic innervation from the pterygopalatine ganglion, which appears to utilize vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) to increase choroidal blood flow. The present studies were undertaken to elucidate the anatomical and neurotransmitter organization of the pterygopalatine ganglion input to orbital and choroidal blood vessels in pigeons. Single- or double-label immunohistochemistry were employed on paraformaldehyde-fixed cryostat sections of the pigeon eye and surrounding orbital tissue to localize 1) VIP+ neurons and fibers; 2) choline acetyltransferase (CHAT)-containing cholinergic neurons and fibers; 3) axons containing the 3A10 neurofilament-associated antigen; and 4) neuronal NO synthase (nNOS)-containing neurons and fibers. NOS+ neurons and fibers were also identified by NADPH-diaphorase histochemistry in sections and whole-mount specimens. The pterygopalatine ganglion was found to consist of an interconnected series of three to four main microganglia of about 50-200 neurons each and numerous lesser microganglia. The major microganglia of the pterygopalatine network in pigeon lie along the superior aspect of the Harderian gland, with many additional fibers and microganglia of the network encircling the gland. Neurons of all microganglia were extremely rich in VIP, nNOS, and NADPH-diaphorase and moderate in CHAT. The majority of the pterygopalatine ganglion neurons were observed to co-contain VIP and nNOS. Axons labeled for VIP, nNOS, NADPH-diaphorase, or the 3A10 antigen could be traced from the pterygopalatine ganglion network to perivascular fiber plexi on orbital blood vessels. These orbital vessels, many of which enter the choroid posteriorly and nasally, appear to be a conduit by which pterygopalatine postganglionic fibers reach the choroid. The pterygopalatine postganglionic fibers were also seen to innervate the Harderian gland and contribute branches to the nearby ophthalmic nerve. Within the choroid, VIP+ fibers were widely scattered and sparse but were most abundant in nasal choroid. A few VIP+ and NADPH- diaphorase+ neurons were also observed in the choroid. These results suggest that pterygopalatine ganglion neurons of birds use VIP and NO to exert vasodilatory control over blood flow to and within the avian choroid.

Animals↗

Immunohistochemical study of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) in choroid plexus papilloma.

Insulin-like growth factor-II (IGF-II), a mitogen for various kinds of cells, has been shown to be secreted from the choroid plexus in animals. Insulin-like growth factor binding protein-2 (IGFBP-2), one of the six carrier proteins for IGFs, is also thought to be released from the choroid plexus, bind to IGF-II in the cerebrospinal fluid (CSF) and modulate the action of this growth factor. Little is known about the expression and localization of these substances in human choroid plexus and choroid plexus papillomas. The present immunohistochemical study demonstrated all six choroid plexus papillomas were positive for IGF-II, whereas normal choroid plexuses were negative for IGF-II. On the other hand, IGFBP-2 was positive in the endothelium and vascular media in the normal choroid plexus, while it was weakly positive in four and negative in two out of six choroid plexus papillomas. These results suggest that the alterations in the IGF-II/IGFBP-2 axis might be involved in the tumorigenesis of choroid plexus papilloma.

Brain Neoplasms↗

Immunohistochemical evidence of endothelin-1 in human choroid plexus.

An immunohistochemical investigation was carried out on 17 specimens of human choroid plexus obtained post mortem, 1 biopsy of normal choroid plexus including part of the lateral ventricle and 1 papilloma of the choroid plexus removed surgically. The material was fixed in formalin. Paraffin and cryostat sections were used. A polyclonal antiserum to endothelin-1 served as a primary antibody. The avidin-biotin-peroxidase method was applied to demonstrate the immunoreaction. The epithelial cells of the choroid plexuses, the choroid papilloma and most ependymal cells of the lateral ventricle showed a distinct brown reaction product in their cytoplasm indicating antigenic sites to endothelin-1. The reaction was of lesser intensity in the ependymal cells. The connective tissue in choroid plexus was unstained. A positive immunoreaction was present in the walls of some vessels in the choroid plexus in cryostat sections. This is the first report on the presence of antigenic sites to endothelin-1 in the epithelial cells of the human choroid plexus. The role of endothelin in these cells should be investigated to ascertain if the cells synthesize this biologically active peptide or if it is merely bound to receptors in them.

Adult↗

Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children.

Choroid plexus tumors are papillary neoplasms originating from the epithelium of the choroid plexus within the cerebral ventricles. They may be highly proliferative tumors, but detailed studies confirming their proliferative potential are lacking. Accordingly, we performed a clinicopathological correlation study of neoplasms arising from the choroid plexus in children using immunohistochemistry to characterize both their proliferative potential and their degree of cell cycle dysregulation when compared to non-neoplastic choroid epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997. The outcome and survival of these children following treatment was determined from the medical record. Immunohistochemical studies were performed on CPPs and CPCs in this patient population and on non-neoplastic choroid epithelium using antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F-1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry at a second surgery after cycles of chemotherapy had been given. The mean survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a minimum follow-up of 4 years for the group. The expression of cell cycle markers and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04 for patients who have died from their disease (P<0.05). We conclude that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to decrease their proliferative potential and expression of cell cycle regulatory proteins.

Adolescent↗