Chromosomal Imbalances in Choroid Plexus Tumors
2002; Elsevier BV; Volume: 160; Issue: 3 Linguagem: Inglês
10.1016/s0002-9440(10)64931-0
ISSN1525-2191
AutoresChristian Rickert, Otmar D. Wiestler, Werner Paulus,
Tópico(s)Glioma Diagnosis and Treatment
ResumoWe studied 49 choroid plexus tumors by comparative genomic hybridization. Chromosomal imbalances were found in 32 of 34 choroid plexus papillomas and 15 of 15 choroid plexus carcinomas. Choroid plexus papillomas frequently showed +7q (65%), +5q (62%), +7p (59%), +5p (56%), +9p (50%), +9q (41%), +12p, +12q (38%), and +8q (35%) as well as −10q (56%), −10p, and −22q (47%); choroid plexus carcinomas mainly showed +12p, +12q, +20p (60%), +1, +4q, +20q (53%), +4p (47%), +8q, +14q (40%), +7q, +9p, +21 (33%) as well as −22q (73%), −5q (40%), −5p, and −18q (33%). Several chromosomal imbalance differences could be found that were characteristic for a tumor entity or age group. In choroid plexus papillomas +5q, +6q, +7q, +9q, +15q, +18q, and −21q were significantly more common whereas choroid plexus carcinomas were characterized by +1, +4q, +10, +14q, +20q, +21q, −5q, −9p, −11, −15q, and −18q. Among choroid plexus papillomas, children more often showed +8q, +14q, +12, and +20q; adults mainly presented with +5q, +6q, +15q, +18q, and −22q. Although the number of aberrations overall as well as of gains and losses on their own bore no significance on survival among choroid plexus tumors, a significantly longer survival among patients with choroid plexus carcinomas was associated with +9p and −10q. Our results show that aberrations differ between choroid plexus papillomas and choroid plexus carcinomas as well as between pediatric and adult choroid plexus papillomas, supporting the notion of different genetic pathways. Furthermore, gain of 9p and loss of 10q seem to be correlated with a more favorable prognosis in choroid plexus carcinomas. We studied 49 choroid plexus tumors by comparative genomic hybridization. Chromosomal imbalances were found in 32 of 34 choroid plexus papillomas and 15 of 15 choroid plexus carcinomas. Choroid plexus papillomas frequently showed +7q (65%), +5q (62%), +7p (59%), +5p (56%), +9p (50%), +9q (41%), +12p, +12q (38%), and +8q (35%) as well as −10q (56%), −10p, and −22q (47%); choroid plexus carcinomas mainly showed +12p, +12q, +20p (60%), +1, +4q, +20q (53%), +4p (47%), +8q, +14q (40%), +7q, +9p, +21 (33%) as well as −22q (73%), −5q (40%), −5p, and −18q (33%). Several chromosomal imbalance differences could be found that were characteristic for a tumor entity or age group. In choroid plexus papillomas +5q, +6q, +7q, +9q, +15q, +18q, and −21q were significantly more common whereas choroid plexus carcinomas were characterized by +1, +4q, +10, +14q, +20q, +21q, −5q, −9p, −11, −15q, and −18q. Among choroid plexus papillomas, children more often showed +8q, +14q, +12, and +20q; adults mainly presented with +5q, +6q, +15q, +18q, and −22q. Although the number of aberrations overall as well as of gains and losses on their own bore no significance on survival among choroid plexus tumors, a significantly longer survival among patients with choroid plexus carcinomas was associated with +9p and −10q. Our results show that aberrations differ between choroid plexus papillomas and choroid plexus carcinomas as well as between pediatric and adult choroid plexus papillomas, supporting the notion of different genetic pathways. Furthermore, gain of 9p and loss of 10q seem to be correlated with a more favorable prognosis in choroid plexus carcinomas. Choroid plexus tumors are intraventricular papillary neoplasms derived from choroid plexus epithelium. These rare tumors account for only 0.4 to 0.6% of all intracranial neoplasms1Aguzzi A Brandner S Paulus W Choroid plexus tumours.in: Kleihues P Cavenee WK Pathology and Genetics. Tumours of the Nervous System. WHO, Lyon2000: 84-86Google Scholar and occur most often in childhood in which they constitute 2 to 3% of tumors in children younger than 15 years of age,2Rickert CH Paulus W Epidemiology of central nervous system neoplasms in childhood and adolescence based on the new WHO classification of nervous system tumors.Child's Nerv Syst. 2001; 17: 503-511Crossref Scopus (362) Google Scholar 4.3% in children younger than 4-years-old, and 13.1% in the first year of life.3Rickert CH Probst-Cousin S Gullotta F Primary intracranial neoplasms of infancy and childhood.Child's Nerv Syst. 1997; 13: 507-513Crossref Scopus (87) Google Scholar Investigations on genetic properties of choroid plexus tumors have so far only been undertaken on ∼20 specimens, mainly in the setting of case reports4Blamires TL Maher ER Choroid plexus papilloma. 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Its main advantage is that it bypasses the need for laborious cell culture to harvest metaphase spreads, and that it can be applied to archival material. No CGH study has hitherto been undertaken on choroid plexus papillomas and carcinomas. To screen for DNA copy number changes that may be involved in tumorigenesis of choroid plexus tumors, we performed a CGH analysis on 34 choroid plexus papillomas and 15 choroid plexus carcinomas. Formalin-fixed and paraffin-embedded biopsy specimens of 49 primary choroid plexus tumors (26 males, 23 females; mean age, 22.7 years; range, 2 months to 73 years) were investigated (Table 1). These consisted of 34 choroid plexus papillomas World Health Organization (WHO) grade I (19 males, 15 females; mean age, 29.9 years; range, 2 months to 73 years) and 15 choroid plexus carcinomas WHO grade III (7 males, 8 females; mean age, 6.2 years; range, 5 months to 28 years). Of these, 22 tumors were located in the lateral ventricles (12 choroid plexus papillomas, 10 choroid plexus carcinomas), 5 in the third ventricle (3 choroid plexus papillomas, 2 choroid plexus carcinomas), and 22 in the fourth ventricle (19 choroid plexus papillomas, 3 choroid plexus carcinomas). All patients underwent primary surgery. A combination of postoperative radiation therapy plus chemotherapy was applied in 5 patients, whereas 3 patients underwent radiation therapy and 7 patients chemotherapy alone; 34 did not receive any adjuvant therapy (Table 1). Clinical follow-up data were available for all 49 patients.Table 1Summary of Clinical DataCaseAgeSexMIB-1LocationAdjThOPClinical courseSurvivalChoroid plexus papillomas (WHO grade I)12 mF4.3Lateral ventricle—TFree of disease>2424 mM30.6Left ventricle—TRecurrence (6 months)>1437 mF3.9Right ventricle—TFree of disease>5749 mF15.4Lateral ventricle—TFree of disease>14511 mF16.3Lateral ventricle—TFree of disease>70612 mF11.1Lateral ventricle—TFree of disease>12723 mF2.1Left ventricle—TFree of disease>20811M2.34th ventricle—TFree of disease>42911M3.54th ventricle—STStable disease>371012F0.5Left ventricle—TFree of disease>201112M0.6Lateral ventricle—TFree of disease>971212M1.3Lateral ventricle—TFree of disease>1241323F8.64th ventricle—TFree of disease>361425M3.63rd ventricleRSTRecurrences (48/84 months)>891526M6.74th ventricleR/CSTRecurrences (46/71 months)>721627F1.44th ventricle—TFree of disease>71729M0.64th ventricle—TFree of disease>441829M13.03rd ventricleRPRecurrence (12 months)211931M0.54th ventricle—TFree of disease>202034F0.84th ventricle—TFree of disease>292136M13.24th ventricle—STRecurrences (38/86 months)1322237M1.34th ventricle—TFree of disease>362338M7.54th ventricle—TFree of disease>242439M3.94th ventricle—TFree of disease>422544M0.2Left ventricle—TFree of disease>692644M3.64th ventricle—TFree of disease>502746F3.94th ventricle—TFree of disease>172856M0.63rd ventricle—TFree of disease>322958F7.9Lateral ventricle—TRecurrence (132 months)>1323059M5.24th ventricle—TFree of disease>363162M3.84th ventricle—STStable disease>483266F0.24th ventricle—PStable disease>253371F0.84th ventricle—TFree of disease>1273473F1.24th ventricle—TFree of disease>43Choroid plexus carcinomas (WHO grade III)355 mM72.2Lateral ventricleCSTRecurrences (3/7 months)>57369 mF30.4Right ventricleCSTRecurrence (4 months)>43711 mF36.5Right ventricleCTRecurrence (12 months)133811 mM64.8Lateral ventricle—PProgress53912 mF34.04th ventricleCTRecurrence (8 months)>204020 mF59.7Lateral ventricle—STProgress74129 mF49.6Right ventricleCTRecurrences (50/53 months)>754239 mM10.0Right ventricleR/CTFree of disease>174339 mM21.5Left ventricleCTRecurrence (14 months)22448M8.6Right ventricleR/CSTStable disease>72459M16.3Left ventricle—STRecurrence (10 months)324610F20.83rd ventricleR/CSTRecurrence (5 months)>64710F23.34th ventricleR/CSTStable disease>124814M15.43rd ventricleCTRecurrence (54 months)>544928F6.04th ventricleRTFree of disease>36Age: in years; m, months.M, male; F, female; MIB-1, proliferation index in per cent; AdjTh, adjuvant therapy after tumor resection; R, radiotherapy; C, chemotherapy; OP, operation; T, total; ST, subtotal; P, partial.Survival: survival in months, >: still alive at time of reporting. Open table in a new tab Age: in years; m, months. M, male; F, female; MIB-1, proliferation index in per cent; AdjTh, adjuvant therapy after tumor resection; R, radiotherapy; C, chemotherapy; OP, operation; T, total; ST, subtotal; P, partial. Survival: survival in months, >: still alive at time of reporting. Histological criteria for classifying a tumor as choroid plexus papilloma or carcinoma were those of the WHO classification.1Aguzzi A Brandner S Paulus W Choroid plexus tumours.in: Kleihues P Cavenee WK Pathology and Genetics. Tumours of the Nervous System. WHO, Lyon2000: 84-86Google Scholar Briefly, plexus papillomas are characterized by fibrovascular connective tissue fronds covered by a single layer of uniform cuboidal to columnar epithelial cells without conspicuous mitotic activity, brain invasion, and necroses, whereas plexus carcinomas show frank signs of malignancy with nuclear pleomorphism, frequent mitoses, blurring of the papillary pattern with poorly structured sheets of tumor cells, necrotic areas, and often diffuse brain invasion. Routine hematoxylin and eosin staining and immunohistochemistry using an avidin-biotin complex technique and antibodies against glial fibrillary acid protein, cytokeratins, S-100 protein, vimentin, prealbumin/transthyretin, neurofilament, neuron-specific enolase, synaptophysin, epithelial membrane antigen, and smooth-muscle actin as well as the proliferation antigen Ki-67 were performed. Diagnoses were made by two neuropathologists (CHR, WP). In addition, the majority of tumors, in particular the choroid plexus carcinomas, had been seen and diagnosed by the German Brain Tumor Reference Center (OD Wiestler, Bonn, Germany). Statistical analysis was performed using Student's t-test, Fisher's exact test, Kaplan-Meier estimates of survival probabilities and log-rank test where applicable. DNA was isolated by phenol-chloroform extraction according to standard protocols. With minor modifications, CGH analysis was performed as described previously.19Rickert CH Sträter R Kaatsch P Wassmann H Jürgens H Dockhorn-Dworniczak B Paulus W Pediatric high-grade astrocytomas show chromosomal imbalances distinct from adult cases.Am J Pathol. 2001; 158: 1525-1532Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar Briefly, tumor DNA was labeled with biotin-16-dUTP (Boehringer Mannheim, Mannheim, Germany) and reference DNA from a healthy male donor with digoxigenin-11-dUTP (Boehringer Mannheim) in a standard nick translation reaction. The DNase concentration in the labeling reaction was adjusted to reveal an average fragment size of 200 to 500 bp. Labeled DNA fragments were purified from remaining nucleotides by column chromatography. For CGH, 500 ng of tumor DNA, 300 ng of reference DNA, and 30 μg of human Cot1 DNA (Gibco, Karlsruhe, Germany) were co-precipitated and redissolved in 10 μl of hybridization buffer. Denaturation of DNA (75°C for 5 minutes) was followed by a preannealing step of 45 minutes at 37°C. Target metaphase spreads (46,XY), which had been prepared following standard procedures, were denatured separately in 70% formamide/2× standard saline citrate for 2 minutes at 72°C. Hybridization was allowed to proceed for 3 to 4 days. Posthybridization washes were performed at a stringency of 50% formamide/2× standard saline citrate at 45°C and 0.1× standard saline citrate at 60°C. Biotinylated and digoxigenated sequences were detected simultaneously, using avidin-fluorescein isothiocyanate (1:200, Boehringer Mannheim) and anti-digoxigenin-rhodamine (1:40, Boehringer Mannheim). The slides were counterstained with 4,6-diamidino-2-phenylindole and mounted in an anti-fade solution (Vectashield, Vector Laboratories, Birmingham, AL, USA). Separate digitized gray level images of 4,6-diamidino-2-phenylindole, fluorescein isothiocyanate, and rhodamine fluorescence were taken with a charge-coupled device camera connected to a Leica DMRBE microscope. Image processing was performed using the Applied Imaging Software. Average green-red ratios were calculated for each chromosome in at least 10 metaphases. Chromosomal regions with CGH ratio profiles surpassing the 50% CGH thresholds (upper threshold, 1.25; lower threshold, 0.75) were defined as loci with copy number gains or losses. Based on experiments with normal control DNA, these thresholds have been shown to eliminate false-positive results. These values have been used in several studies comparing CGH data with results obtained by other cytogenetic methods and have proven to provide robust criteria for the diagnosis of chromosomal gains and losses. Overrepresentations were diagnosed as high-level gains when the fluorescence intensity levels exceeded 1.5 or when the fluorescein isothiocyanate fluorescence showed strong focal signals. For the assignment of these high-level gains to chromosomal bands, the signal intensities were compared to the 4,6-diamidino-2-phenylindole banding on individual chromosomes. As tumor specimens and normal DNA were not sex matched, X and Y chromosomes were excluded. Also excluded were centromeric and satellite regions of the acrocentric chromosomes and chromosome 19 because of the abundance of highly repetitive DNA sequences as well as the frequent occurrence of false-positive CGH results as shown by interphase fluorescence in situ hybridization using suitable DNA probes. CGH revealed DNA copy number changes in 32 of 34 choroid plexus papillomas and 15 of 15 choroid plexus carcinomas; six patients showed either only gains or only losses (Table 2). Every chromosome was shown to carry imbalances (Figure 1). The highest number of DNA copy number changes was detected in a choroid plexus carcinoma (case 41, 26 imbalances), the lowest in two choroid plexus papillomas (cases 2 and 18, none) (Table 2). Choroid plexus papillomas showed an average of 7.3 chromosomal changes per tumor (range, 0 to 14; 4.6 gains versus 2.7 losses), choroid plexus carcinomas an average of 10.7 imbalances per tumor (not significant; range, 1 to 26; 6.4 gains versus 4.3 losses) (Table 1, Figure 1). Choroid plexus papillomas exhibited significantly fewer high-level gains per tumor compared to choroid plexus carcinomas (0.5 versus 2.9, P < 0.05) (Table 1, Figure 1). Gains were more common than losses in both entities (not significant).Table 2Summary of CGH FindingsCaseGains (+, respective top lines) and losses (−, respective bottom lines)Choroid plexus papillomas (WHO grade I)1+2, 12, 13q, 20−1, 3, 4, 5, 9, 10, 22q2+None−None3+7, 8, 12−104+8, 12, 13q, 14q, 15q, 20−1, 3, 4, 6, 105+2, 7, 9, 12, 14q31-qter, 20−3, 6, 106+7q11.2-31, 8q11.2-22, 12q12-21−1p, 1q42-qter, 3p22-pter, 3q, 4q32-qter, 5p15.1-pter, 5q, 6q22.2-qter, 10, 13q31-qter7+4q12-32, 7, 8, 12p, 12q12-15−10, 17, 22q8+5, 7, 9, 11, 12−21q9+5p12-14, 5q11.2-23, 7, 8q11.2-24.1, 9, 12p,12q12-22−16, 17p, 20q, 21q, 22q10+5, 7, 8, 9, 12, 14q31-qter, 15q, 18, 20−3, 10, 13q11+5p12-14, 5q11.2-23, 7, 8, 9, 12p, 12q12-22, 18−21q12+7−None13+7, 15q, 17q24-qter, 18, 20q13.1-qter, 22q13−2, 1014+7, 13q−3, 1015+5, 15q22-qter−None16+6, 9, 12−10, 13q, 14q, 15q, 18, 21q, 22q17+5, 9, 13q, 18−2, 10q, 22q18+None−None19+5 (p+q11.2-23), 8−10, 11q, 12q23-qter, 22q12-qter20+4, 5p, 5q11.2-23, 7, 20−22q21+5, 7, 9, 15q, 18−21q, 22q12-qter22+5p12-14, 5q11.2-23, 6, 7p, 7q11.2-31, 8q11.2-22,9p, 9q12-22, 15q, 18p−12q24.1-qter, 16, 17, 2023+4, 5p12-14, 5q11.2-23, 7p, 7q11.2-31.2, 15q−22q24+5, 9p, 9q12-31, 15q, 18−10, 14q, 21q, 22q25+7, 9, 12p, 12q12-22−None26+5, 7p, 17, 20−21q27+5p12-14, 5q11.2-23, 6q13-24, 7p21-pter, 7q21-31, 9p, 12p, 15q−10, 13q, 18, 21q28+4, 5p12-14, 5q11.2-23, 7q11.2-31, 13q, 15q, 18−1029+5p, 5q11.2-21, 6q13-24, 8q13-22−2, 10q, 16, 17, 22q30+5q, 7, 9, 18−1, 6, 10, 16, 22q31+3, 5, 7q, 9, 20−10, 22q12-qter32+5q11.2-23, 6q12-24, 7, 8q11.2-24.1, 9p, 12p,12q12-22−10q25-qter, 17, 22q33+5p12-14, 5q11.2-23, 7, 8, 9−22q12-qter34+5p12-14, 5q11.2-23, 9p−17, 22q13Choroid plexus carcinomas (WHO grade III)35+1p12-31, 1q, 2, 5, 7, 10, 12 (p+q12-21), 13q, 14, 18, 20−3, 4, 6, 8, 9, 11, 15, 16, 17, 22q36+1, 4, 20p, 21q−22q1337+None−4, 22q12-qter38+1, 2p, 3q25-qter, 10, 12, 14q, 18, 20, 21q−3p, 4q, 5, 6, 7, 8q, 13q21-qter39+None−22q12-qter40+1, 2p (22-pter), 2q (24-31), 4q, 7 (q11.2-32), 10p, 12, 14q, 20q−5, 6, 8, 9, 11, 15q, 16, 17p, 18, 22q41+1, 2p (22-pter), 2q (24-31), 3p22-pter, 4p, 7q, 8q (21.1-qter), 10, 12p, 12q12-23, 14q11.2-23, 15q22-qter, 20p, 20q, 21q22−3q, 5, 6, 7p, 9, 11, 13q, 16, 17, 18, 22q42+1, 4, 7q11.2-32, 9, 20, 21q−5, 15q, 17, 1843+1, 5p, 8q, 10q23-qter, 12, 14q, 20−5q11.2-32, 9p, 18q, 22q44+4q12-28, 5q11.2-23, 7, 8q11.2-22, 9p−2, 3, 10, 15q, 18q45+1p31-pter, 1q (21-25), 4p, 4q12-26, 8, 12, 14q, 17q, 20, 21q−2, 3, 4q31.1-qter, 5, 1146+4, 8q11.2-24.1, 9p, 12p, 12q12-23−10, 22q47+None−22q12-qter48+4, 8, 9, 11, 12p, 12q12-22, 17, 20−10, 13q, 22q49+4, 6p, 8, 9p, 11, 12, 20p−10, 22qUnderlined: high level gains. Open table in a new tab Underlined: high level gains. The most common DNA copy number changes overall were gains of 7q (55%), 5q, 7p (47%), 9p, 12p, 12q (45%), 5p (43%), 8q (37%), 9q, 20p, and 20q (33%), as well as of losses of 22q (55%), 10q (47%), and 10p (37%). Choroid plexus papillomas frequently showed +7q (65%), +5q (62%), +7p (59%), +5p (56%), +9p (50%), +9q (41%), +12p, +12q (38%), and +8q (35%) as well as −10q (56%), −10p, and −22q (47%); choroid plexus carcinomas mainly showed +12p, +12q, +20p (60%), +1, +4q, +20q (53%), +4p (47%), +8q, +14q (40%), +7q, +9p, +21 (33%), as well as −22q (73%), −5q (40%), −5p, and −18q (33%). Minimal common regions found in at least five plexus tumors of each entity mapped to +7q21-31.2 (22 tumors), +5q11.2-22 (21 tumors), +7p21-pter (20 tumors), −10q25-qter (19 tumors), +5p12-14 (19 tumors), −22q13 (16 tumors), +9q12-22 (14 tumors), +12q12-15 (13 tumors), +8q13-22 (12 tumors), +15q22-qter (10 tumors), −3p22-pter (6 tumors) in choroid plexus papillomas; and to −22q13 (11 tumors), +12q12-22 (9 tumors), +1p31-pter (8 tumors), +4q12-26 (8 tumors), −5q11.2-32 (6 tumors), +8q21.1-22 (6 tumors), +14q11.2-23 (6 tumors), +21q22 (5 tumors), +7q11.2-32 (5 tumors) in choroid plexus carcinomas. In choroid plexus papillomas high-level gains were located on chromosomes 7 (5 cases), 9 (4 cases), 15q (3 cases), 5, 8 (2 cases), 12, and 20 (1 case); in carcinomas on 20q (6 cases), 1 (5 cases), 2p, 12, 20p (4 cases), 2q, 14q (3 cases) 4q, 8, 10q, 18, 21q (2 cases), 3q, 4p, 5p, 7q, 9p, 10p, 13q, and 17p (1 case). Comparing the distribution and frequency of specific chromosomal imbalances between choroid plexus papillomas and carcinomas, and between pediatric and adult papillomas to establish chromosomal imbalances characteristic for a tumor entity or age group, the following significant differences could be found (relative frequencies and P value are in parentheses): 1) In choroid plexus papillomas, +5q (62% versus 7%, P < 0.0005), +6q (15% versus 0%, P < 0.05), +7q (65% versus 33%, P < 0.03), +9q (41% versus 13%, P < 0.03), +15q (29% versus 7%, P < 0.05), +18q (24% versus 13%, P < 0.05), and −21q (24% versus 0%, P < 0.005) were significantly more common whereas choroid plexus carcinomas were characterized by +1 (53% versus 0%, P < 0.0005), +4q (53% versus 12%, P < 0.003), +10 (33% versus 0%, P < 0.005), +14q (40% versus 9%, P < 0.005), +20q (53% versus 24%, P < 0.003), +21q (33% versus 0%, P < 0.005), −5q (40% versus 6%, P < 0.005), −9p (27% versus 3%, P < 0.01), −11 (27% versus 3%, P < 0.01), −15q (27% versus 3%, P < 0.01), and −18q (33% versus 3%, P < 0.005). 2) Among choroid plexus papillomas, children (patients younger than 18 years of age) significantly more often showed +8q (58% versus 23%, P < 0.001), +14q (25% versus 0%, P < 0.01), +12 (83% versus 18%, P < 0.0005), and +20q (33% versus 18%, P < 0.01) whereas adults mainly presented with +5q (77% versus 33%, P < 0.005), +6q (23% versus 0%, P < 0.01), +15q (36% versus 17%, P < 0.005), +18q (27% versus 17%, P < 0.01), and −22q (59% versus 25%, P < 0.001). The mean MIB-1 proliferation indices were significantly different between choroid plexus papillomas (mean, 5.3%; SD, 6.4%) and choroid plexus carcinomas (mean, 31.3%; SD, 21.3%; P < 0.0005). Among the choroid plexus carcinomas, the mean MIB-1 proliferation indices were significantly higher in patients younger than 3 years of age (mean, 49.6%) compared to the age group older than 3 years (mean, 15.2%; P < 0.001). Furthermore, the mean ages of patients were significantly different between choroid plexus papillomas and choroid plexus carcinomas (mean, 29.9 years versus 6.2 years; P < 0.000005). As to the tumor site, there was prevalence for the fourth ventricle among choroid plexus papillomas (56% versus 20% in carcinomas) and for the lateral ventricles among choroid plexus carcinomas (67% versus 35% in papillomas). Among choroid plexus papillomas, tumor location was age-dependent: the lateral ventricles were significantly more often involved in younger patients (mean, 12.0 years) compared with the fourth ventricle (mean, 40.2 years; P < 0.0005). Additionally, there was a female prevalence for the lateral (8 versus 4 patients) and a male prevalence for the fourth ventricle (12 versus 7) among choroid plexus papillomas whereas the opposite was the case for choroid plexus carcinomas (6 versus 4 and 0 versus 3, respectively). MIB-1 proliferation indices were higher, albeit not significantly, among lateral ventricle tumors compared with fourth ventricle tumors, regardless of tumor entity (choroid plexus papillomas, 7.9% versus 3.6%; choroid plexus carcinomas, 37.0% versus 21.1%, respectively). Among all plexus tumors, patient age increased and proliferation decreased with more caudal location: 7.9 years and 21.1% in the lateral ventricles, 26.8 years and 10.7% in the third ventricle, and 36.5 years and 6.0% in the fourth ventricle. Clinical follow-up data were available for all 49 patients. At the time of reporting, 2 of 34 patients with choroid plexus papillomas (5.9%) and 5 of 15 patients with choroid plexus carcinomas had died of their disease (33.0%). The respective 1-, 3-, and 5-year survival rates were 100%, 95%, and 90% for choroid plexus papillomas and 85%, 44%, and 28% for choroid plexus carcinomas. Although the number of aberrations overall as well as of gains and losses bore no significance on survival among choroid plexus tumors, a significantly longer survival among patients with choroid plexus carcinomas was associated with +9p and −10q: comparing the five patients who had succumbed to their disease with the five long-term survivors (>24 months), Fisher's exact test for small sample sizes revealed the significance level to be P = 0.048 for each of the above aberrations, whereas Kaplan-Meier estimates of survival probabilities and consecutive log-rank tests calculated the significance level to be P = 0.0186 each. Furthermore, deceased carcinoma patients tended to be younger at tumor diagnosis than long-term survivors (3.2 years versus 10.6 years, not significant) and their tumors showed higher MIB1 proliferation indices (39.8% versus 30.4%, not significant). Molecular genetic data about choroid plexus tumors are scarce. 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