|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2003 American Society for Clinical Oncology New Classification Scheme for the Prognostic Stratification of Meningioma on the Basis of Chromosome 14 Abnormalities, Patient Age, and Tumor Histopathology
From the Neurosurgery Service, Pathology Service, and Unidad de Investigación, Hospital Universitario de Salamanca; and Centro de Investigaciones del Cáncer, Cytometry General Service and Department of Medicine, University of Salamanca; Salamanca, Spain. Address reprint requests to Angel Maíllo, MD, Servicio de Neurocirugía, Hospital Universitario de Salamanca, Paseo de San Vicente 58, 37007 Salamanca, Spain; e-mail: a_maillo{at}yahoo.es.
Purpose: Meningiomas are usually considered benign tumors. However, relapses occur in 10% to 20% of all patients, including both histopathologically aggressive and benign tumors. This study explored the value of numerical abnormalities for 10 different chromosomes in meningiomas for predicting relapse-free survival (RFS). Patients and Methods: This study prospectively analyzed the frequency of numerical abnormalities of chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in 70 meningioma patients by fluorescence in situ hybridization and their relationship with disease characteristics at diagnosis and patients’ outcome. Results: Results showed the presence of numerical abnormalities for one or more chromosomes in most patients (77%). Chromosome 22 in the whole series and chromosome Y in males were those more frequently altered, followed by chromosomes 1, 14, and X in females. Patients with abnormalities of chromosomes 1, 9, 10, 11, 14, 15, 17, the sex chromosomes, and gains of chromosome 22 were associated with adverse prognostic features, more frequent relapses, and shorter RFS. Multivariate analysis showed that tumor grade together with chromosome 14 status and age were the best combination of independent variables for predicting RFS. According to these variables, all patients with a score of two or more than two adverse prognostic factors had experienced relapse at 5 years, whereas none of those with a score of zero had experienced relapse 10 years after surgery. Conclusion: In addition to age and histologic grade, abnormalities of chromosome 14 contribute to a better prognostic stratification of meningioma patients at diagnosis. Additional prospective studies in larger series of patients, also including larger numbers of patients who experienced relapse, are necessary to confirm the utility of the proposed predictive model.
MENINGIOMAS ARE generally considered to be histologically benign tumors. Despite this, recurrences occur in up to 10% to 20% of the patients after curative surgery. Such relapses involve not only patients with aggressive histologic grades (grades 2 and 3 of the World Health Organization classification1), but also histologically benign tumors. To date, no parameters have been identified that could help to predict these relapses, and therefore, an important challenge still remains in meningioma tumor research to find a way to discriminate at diagnosis between patients who will be cured and those who are at a high risk of relapse. Apart from histologic grade2–6 and age,7 few other disease features (ie, the DNA ploidy status and the fraction of S-phase tumor cells) have shown to be of use for predicting recurrences in meningioma patients. Interestingly, many of these latter disease characteristics that have been associated with prognosis in meningioma reflect, at least to a certain extent, the presence of underlying genetic abnormalities in the neoplastic cells,8–14 which change the overall DNA contents or the proliferative rate of tumor cells. In recent years, an increasing number of studies have analyzed the cytogenetic abnormalities present in meningioma tumors. Such studies, in which fluorescence in situ hybridization (FISH) and molecular techniques were employed along with conventional cytogenetic methods, have shown clearly that the presence of monosomy 22/22q- is the most frequent single chromosome abnormality in meningiomas.15–30 However, the clinical significance of the complete or partial loss of one copy of chromosome 22 still remains unclear. Accordingly, although the loss of genetic material on chromosome 22 has been considered to be an early step in the development of meningiomas,31 such abnormalities have not been found to correlate with any particular clinical behavior.18,24,32–39 In a recent study that was based on a large series of meningioma tumors, we showed that gains of chromosome 22, in the context of an hyperdiploid karyotype, but not monosomy 22/22q-, did correlate with a worse clinical outcome.40 These results indicate that additional numerical chromosomal abnormalities, other than gains of chromosome 22, might also be associated with a different clinical behavior of the tumor, and might help to predict disease outcome. The aim of this study is to explore the prognostic value of numerical abnormalities of 10 different chromosomes in a series of 70 meningioma patients observed for a median period of more than 5 years. Our results show that numerical abnormalities of chromosome 14/14q- represent an independent prognostic factor that, together with the histologic grade of the tumor and age at diagnosis, contributes to the identification of groups of meningioma patients at a significantly different risk of relapse.
Patients A total of 70 consecutive patients, 31% males and 69% females with a mean age of 56 ± 15 years (range, 16 to 81 years), who were diagnosed of meningioma at the Neurosurgical Service of the University Hospital of Salamanca between 1990 and 1995, were analyzed in the present study. All patients were diagnosed with either intracranial (93%) or spinal (7%) meningiomas after surgery. Intracranial tumor localization was distributed as follows: cranial base including posterior fossa, 39%; cerebral convexity, 24%; parasagittal and tentorial, 26%; and ventricular, 4%. Patients who did not undergo complete tumor resection, according to Simpson’s grade,41 were excluded from the study. Histologic diagnosis and classification of meningioma were established in all patients using the criteria of the World Health Organization classification.1 According to this classification, 89% of the tumors were classified as grade 1 (including all benign subtypes), 7% were grade 2 (or atypical), and 4% were grade 3 (or anaplastic). Histologic grade of each tumor was confirmed in all samples in a second independent evaluation of tumor histology by an experienced neuropathologist. All tumors studied correspond to first primary meningiomas. When the study was closed in 2001, of the 70 patients analyzed, 16 had experienced a relapse, with a median relapse-free survival (RFS) of 40 months (range, 7 to 124 months). The overall median follow-up of the whole series was 70 months (range, 7 to 145 months). Follow-up controls included, apart from clinical and biologic routine parameters, neuroimaging analysis using axial computerized tomography and magnetic resonance studies for the early detection of relapses. Two patients died as a result of other causes during the follow-up period.
FISH Studies
For the investigation of numerical chromosome abnormalities by interphase FISH, the following commercially available probes (Vysis Inc, Downers Grove, IL, and Q-BIOgene Inc, Carlshad, CA), which have been described extensively in previous publications,44 were used in double stainings: for chromosomes 9 and 22, LSI BCR/ABL dual-color probe; for chromosomes 15 and 17, LSI PML/RAR- For interphase FISH studies, fixed cells were dropped onto slides cleaned with ethanol-ether (1/1, vol/vol) according to conventional cytogenetic protocols. The slides were then sequentially incubated with 0.1 mg/mL pepsin (10 minutes at 37°C), fixed in 1% acid-free formaldehyde (10 minutes at room temperature), and dehydrated in ethanol, as previously described.45 After this procedure, the slides containing DNA from both the cells and the probes were denatured at 75°C (1 minute) and immediately hybridized overnight (37°C) in a Hybrite thermocycler (Vysis Inc). Once this incubation period was completed, slides were sequentially washed (5 minutes at 46°C) in 50% formamide-2XSSC and in phosphate-buffered saline with 1% Tween-20 (vol/vol). Cells were then counterstained with diamino-2-phenylindole (DAPI); Vectashield (Vector Laboratories Inc, Burlingame, CA) was used as antifading agent.
The number of hybridization spots was evaluated using a BX60 fluorescence microscope (Olympus, Hamburg, Germany) equipped with a 100x oil objective; for each slide, at least 200 nuclei were evaluated. For all slides measured, the number of unhybridized cells in the areas assessed was irrelevant (< 1%), and only those spots with a similar size, intensity, and shape were scored. Doublet signals were rarely found ( For each chromosome analyzed, patients were grouped according to the presence or absence of both numerical chromosome gains or losses.
Flow Cytometric Analysis of Cell DNA Contents
Statistical Methods RFS curves were plotted according to the method of Kaplan and Meier, and the one-sided log-rank test was used to establish the statistical significance of the differences observed between curves (survival; SPSS). For the analysis of RFS, this was considered as the time lapse between diagnosis and either recurrence or the last follow-up control for those patients who had recurrence of the disease or remained relapse-free during the study, respectively. Those two patients who died as a result of causes other than meningioma had no recurrence of the tumor and for the analysis of RFS were considered to be relapse-free at the time of the last follow-up study. Multivariate analysis of prognostic factors for RFS was performed using the Cox stepwise regression model (regression, SPSS). The results of this model were attained using forward selection. In this part of the study only those variables showing a significant association with RFS in the univariate analysis were included. Identification of the most discriminant cutoff values for categorization of continuous variables was performed using receiver operating characteristic curve analysis for relapse. Statistical significance was considered to be present once the P values (or, where appropriate, Pearson-corrected P values) obtained were lower than .05.
Fifty-four of the 70 meningioma patients included in this study (77%) displayed numerical abnormalities for at least one of the 10 chromosomes analyzed. The frequency and type of numerical abnormalities detected for each chromosome in these 70 patients has been previously reported in detail.44 Briefly, chromosome 22 in the whole series (61%) and chromosome Y in males (45%) were the more frequently altered chromosomes; the abnormalities mainly corresponded to monosomy 22/22q deletions (37 of 43; 86%), and nulisomy Y (seven of 10; 70%). Other chromosomes were found to be frequently altered in number, including chromosomes 1 (40%), 14 (33%), and X in females (35%); losses of the three chromosomes were more frequent than gains (25% v 15%, 19% v 14%, and 23% v 12%, respectively). The remaining chromosomes analyzed were found to be aberrant at lower frequencies: chromosome 9 was altered in 25% (21% corresponded to chromosome gains); chromosome 10 was altered in 23% (gains were found in 17% and monosomy 10 in 6% of these patients); chromosome 11 was altered in 22% (19% were gains); chromosome 15 was altered in 22% (all corresponding to chromosome gains); chromosome 17 was altered in 24% (23% were gains and 1% corresponded to chromosome losses); and chromosome X was altered in 23% of the males, and all of these patients showed gains of chromosome X.
When the patients were grouped according to the number of copies of each of the 10 chromosomes studied, no significant differences were found with regard to patients’ age and sex distribution among patients with normal chromosome number, chromosome losses, and chromosome gains, except for a higher male-to-female (M/F) ratio found among patients displaying losses for chromosomes 1 (M/F ratio of 2.70 v 0.23 and 0.12 for patients with normal and chromosome 1 gains, respectively; P
As might be expected, a greater incidence of DNA aneuploid status was also found among patients carrying abnormalities for most chromosomes analyzed (Table 2  ). Regarding the cell cycle distribution of meningioma tumor cells, a significant association was observed between the presence of an altered number of copies of chromosomes 10, 15, 17, and 22 and a higher percentage of S-phase tumor cells. In contrast, no association was found between the proportion of S-phase tumor cells and the presence of numerical abnormalities for chromosomes 1, 9 11, 14, and the sex chromosomes (Table 2).
From the prognostic viewpoint, patients displaying either gains of chromosomes 9, 11, 15, 17, and 22 or any abnormality of chromosomes 10 and 14, showed a significantly higher incidence of relapses (P  .02) together with a shorter RFS (P .002; Table 3 and Fig 1). A high degree of association was found for most of these chromosome status–related variables and from all of them only chromosome 14 (P = .03) and chromosome 22 (P = .009) had independent predictive value. Other clinical and biologic disease characteristics that displayed a significant influence on disease outcome included age (median RFS for patients < 45 years of age of 79 v months not reached for older individuals; P = .001), tumor localization (median RFS of ventricular tumors of 53 v > months not reached for the other meningiomas; P = .03), tumor grade (median RFS for grades 1, 2, and 3 tumors not reached, and 36, and 13 months, respectively; P < .0001), tumor proliferation (median RFS for patients with 1.8% 5-phase tumor cells not reached v 82 months for those with > 1.8% 5-phase tumor cells; P = .03), and DNA ploidy status (median RFS not reached v 87 months for diploid and aneuploid tumors; P = .03; Table 3 and Fig 2B). Once multivariate analysis was performed in which both the clinicopathologic and chromosome-associated variables were simultaneously included, it was observed that tumor grade (P < .0001) together with numerical abnormalities for chromosome 14 (P = .03) and age (P = .002) was the best combination of independent variables for predicting RFS in meningioma patients. As shown in Table 4 and Figure 3 from all chromosomes analyzed, chromosome 14 was the only one of additional predictive value to the combined use of age and histologic grade.
On the basis of these results, a prognostic score ranging from 0 to 3 was established for each individual according to the histologic grade of the tumor, patient’s age, and the presence or absence of numerical abnormalities of chromosome 14. Accordingly, grade 1 histology, a normal number of copies of chromosome 14, and age  45 years were considered to score as 0; in turn, grades 2 and 3, presence of an abnormal number of copies of chromosome 14, and age below 45 years scored as 1. According to the score for these variables, meningioma patients could be stratified into three groups with significantly different RFS rates (P < .0001). As shown in Fig 3A , patients scoring two or more adverse prognostic factors (n = 9) all had relapsed at 5 years (median RFS at 5 years of 0% ± 0%; in contrast, none of the 33 patients with a score of 0 had relapsed 10 years after diagnosis (median RFS at 10 years of 100% ± 0%). Patients with score of 1 relapsed more frequently (P = .01) than those with score of 0, with median RFS rates at 5 and 10 years of 82% ± 7% and 70% ± 10%, respectively.
Cytogenetic studies show that meningiomas are relatively heterogeneous tumors that frequently display complex karyotypes. Monosomy 22/22q- is by far the most frequent chromosomal abnormality detected in such tumors,15–30,39,47 as found in this study. Abnormalities involving chromosomes other than 22 have also been reported as frequent in meningiomas. Such abnormalities may involve chromosomes 1, 23,31,35–37,44,47–54 3,23,37 9,31,35,36,44,55 10,31,35,37,44,54–57 11,44,47 14,31,35,37,44,47,49,54,58–61 and 17,31,34,44 as well as the sex chromosomes x and y.62 Despite this, a careful analysis of the literature shows disturbing levels of variability with regard to the exact incidence of such chromosome abnormalities, which probably reflects, at least to a certain extent, the use of different methods—conventional karyotyping versus interphase and metaphase FISH versus molecular techniques—for investigation, or relates to the low number of cases included in some series. The existence of clonal heterogeneity within most of the tumors may also help to explain the variability found in the literature. Such discrepancies also translate into variable and even contradictory results with regard to the prognostic value of the cytogenetic abnormalities in meningiomas. In this study, which is based on a large series of meningioma tumors, we systematically investigated by interphase FISH the presence of numerical abnormalities for a total of 10 different human chromosomes, including those more frequently reported as altered in meningiomas. The systematic use of multicolor stainings with highly efficient probes specific for chromosome regions that are known to be most frequently deleted or gained in meningiomas, increased the sensitivity of the method for the detection of small clones of tumor cells within each tumor; therefore, it allowed a better characterization of each tumor with regard to the presence of numerical chromosome abnormalities. Our major goal was to explore the potential clinical value of these chromosomal abnormalities to identify, at diagnosis, groups of patients at different risks of relapse. Previous studies indicate that numerical chromosomal abnormalities are more frequently found among atypical and anaplastic meningiomas, although they are also observed among patients displaying a benign histopathology,15,27,31,62,63 as found in the present study. In this sense, we also showed the existence of a clear association between the presence of numerical abnormalities for most of the chromosomes analyzed and other disease features that have been associated with a worse clinical outcome,40 including a higher proportion of S-phase tumor cells and, as expected, a greater incidence of DNA aneuploid tumors. In contrast, no clear association was found between the chromosome status and age, tumor localization, or other characteristics of the disease at diagnosis. Interestingly, abnormalities involving loss of either chromosome 1p or chromosome 14q were more frequently observed in males, supporting the notion that different chromosomal instability pathways may be involved in meningiomas developing in male and female patients, as previously suggested by our group.44 Few reports35,49,51,61,64,65 have been published to date that have explored the potential prognostic value of the genetic abnormalities detected at diagnosis for predicting relapse risk in meningiomas. Because surgery might have an influence on tumor regrowth, as opposed to the recurrences themselves, in this study only patients undergoing a complete tumor resection (Simpson’s grade 1, 2, and 3) were analyzed. Publications that are based on the cytogenetic analysis of meningioma tumor samples at relapse indicate that, together with monosomy 22/22q-, total or partial losses of chromosome 115,35,51,52,58,65 and chromosome 1415,49,61 are the most frequently detected abnormalities, the latter being associated with a higher relapse rate among histologically benign patients.49,61 More recently, we have shown (in a large series of meningiomas) that although monosomy 22/22q- deletions did not have a prognostic influence on relapse prediction, gains of chromosome 22 were an independent prognostic factor for predicting RFS. Interestingly, we showed that in those patients carrying trisomy or tetrasomy 22 (or both), complex karyotypes consistent with the existence of additional numerical abnormalities for other chromosomes were found.40 In line with these observations, in this study we confirm that gains of chromosome 22 as well as gains of chromosomes 9, 11, 15, 17, and numerical abnormalities of chromosomes 10 and 14 have prognostic impact on disease outcome. Once we explored the potential added value of these abnormalities to other clinical and biologic prognostic factors, we found that the best combination of independent variables for predicting RFS in meningioma patients included patient age at diagnosis, the histologic grade of the tumor, and the presence or absence of abnormalities for chromosome 14. On the basis of these results, we built a scoring system that allowed the identification of three different patient risk groups with significantly different risks of relapse at 5 (0%, 18%, and 100%) and 10 years (0%, 29%, 100%). Despite the fact that an association has been reported between different chromosomal abnormalities and prognosis in meningiomas,15,23,35,49,51,61,64,65 to the best of our knowledge, this is the first time a scoring system that is based on the combined assessment of patient age, tumor grade, and chromosome 14 abnormalities is proposed that allows identification of both a minor group (13%) of meningiomas with a high incidence of relapses at 5 years (scores 2 and 3) and a major group of patients (47%) who are relapse-free at 10 years (score 0). The prognostic value of histopathology alone is improved, especially among grade 1 tumors. In summary, the results of this study show that the presence of numerical abnormalities of chromosome 14 is an independent adverse prognostic factor in meningioma tumors. Once this variable is combined with tumor histopathology and patient age, different groups of patients with meningioma at a significantly different risk of relapse can be identified at diagnosis. Despite this, our results should be considered to be exploratory because they were based on a relatively limited number of patients and relapses for which multiple comparisons were made; the predictive model proposed has not been tested in a different confirmatory data set. Thus, additional prospective studies in large series of patients, which include also higher numbers of relapses, are necessary to confirm the clinical utility of the new prognostic classification proposed.
Partially supported by grants from the Fondo de Investigaciones Sanitarias (FIS 01/1564 and PI 020010, Madrid, Spain), the Consejeria de Sanidad of the Junta de Castilla-Leon (Acción Biomedicina, Exp 02/02, Valladolid, Spain), and the Fundación memoria de D. Samuel Solorzano Barruso (Salamanca, Spain). M.D.T. is supported by a grant from the programa Ramón y Cajal (Ministerio de Ciencia y Tecnología, Madrid, Spain), and J.M.S. is supported by a grant (02/9103) from Ministerio de Sanidad y Consumo (Madrid, Spain).
1. Louis DN, Scheithauer BW, Budka H, et al: Meningiomas, in Kleihues P, Cavenee WK (eds): Pathology and Genetics of Tumours of the Nervous System. Lyon, France, IARC Press, 2000, pp 176–184 2. de la Monte SM, Flickinger J, Linggood RM: Histopathologic features predicting recurrence of meningiomas following subtotal resection. Am J Surg Pathol 10:836–843, 1986[CrossRef][Medline] 3. Perry A, Scheithauer BW, Stafford SL, et al: "Malignancy" in meningiomas: A clinicopathological study of 116 patients, with grading implications. Cancer 85:2046–2056, 1999[Medline] 4. Maier H, Ofner D, Hittmair A, et al: Classic, atypical, and anaplastic meningioma: Three histopathological subtypes of clinical relevance. J Neurosurg 77:616–623, 1992[Medline] 5. McLean CA, Jolley D, Cukier E, et al: Atypical and malignant meningiomas: Importance of micronecrosis as a prognostic indicator. Histopathology 23:349–353, 1993[Medline] 6. Scarpelli M, Mazzucchelli R, Colanzi P: Meningioma: The impact of new techniques for the diagnosis and prognosis. Adv Clin Path 1:149–153, 1997[Medline] 7. Stafford SL, Perry A, Suman VJ, et al: Primarily resected meningiomas: Outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through 1988. Mayo Clin Proc 73:936–942, 1998[Medline] 8. Akachi K, Matsumoto M, Yasue M, et al: DNA analysis of meningiomas using paraffin-embedded surgical specimens in connection with clinical recurrence. No Shinkei Geka 19:1129–1134, 1991[Medline] 9. Crone KR, Challa VR, Kute TE, et al: Relationship between flow cytometric features and clinical behavior of meningiomas. Neurosurgery 23:720–724, 1988[Medline] 10. Cruz-Sanchez FF, Miquel R, Rossi ML, et al: Clinico-pathological correlations in meningiomas: A DNA and immunohistochemical study. Histol Histopathol 8:1–8, 1993[Medline] 11. Ironside JW, Battersby RD, Lawry J, et al: DNA in meningioma tissues and explant cell cultures: A flow cytometric study with clinicopathological correlates. J Neurosurg 66:588–594, 1987[Medline] 12. Maillo A, Diaz P, Blanco A, et al: Proportion of S-phase tumor cells measured by flow cytometry is an independent prognostic factor in meningioma tumors. Cytometry 38:118–123, 1999[CrossRef][Medline] 13. May PL, Broome JC, Lawry J, et al: The prediction of recurrence in meningiomas: A flow cytometric study of paraffin-embedded archival material. J Neurosurg 71:347–351, 1989[CrossRef][Medline] 14. Yasue M, Akasaki Y, Numoto TR, et al: MIB-1 immunostaining and DNA flow cytometry in meningiomas. Noshuyo Byori 13:17–20, 1996[Medline] 15. Al Saadi A, Latimer F, Madercic M, et al: Cytogenetic studies of human brain tumors and their clinical significance: II. Meningioma. Cancer Genet Cytogenet 26:127–141, 1987[CrossRef][Medline] 16. Blin N, Mullenbach R, Suijkerbuijk R, et al: Cosmid mapping and locus linkage within the human chromosomal region 22q13.1. Cancer Genet Cytogenet 70:108–111, 1993[CrossRef][Medline] 17. Collins VP, Nordenskjold M, Dumanski JP: The molecular genetics of meningiomas. Brain Pathol 1:19–24, 1990[Medline]
18. Dumanski JP, Rouleau GA, Nordenskjold M, et al: Molecular genetic analysis of chromosome 22 in 81 cases of meningioma. Cancer Res 50:5863–5867, 1990 19. Katsuyama J, Papenhausen PR, Herz F, et al: Chromosome abnormalities in meningiomas. Cancer Genet Cytogenet 22:63–68, 1986[CrossRef][Medline] 20. Lekanne Deprez RH, Groen NA, van Biezen NA, et al: A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene. Am J Hum Genet 48:783–790, 1991[Medline] 21. Maltby EL, Ironside JW, Battersby RD: Cytogenetic studies in 50 meningiomas. Cancer Genet Cytogenet 31:199–210, 1988[CrossRef][Medline] 22. Meloni A, Morgan R, Bridge J, et al: Cytogenetic findings in typical and atypical meningioma. Cancer Genet Cytogenet 51:35–39, 1991[CrossRef][Medline] 23. Perry A, Jenkins RB, Dahl RJ, et al: Cytogenetic analysis of aggressive meningiomas: Possible diagnostic and prognostic implications. Cancer 77:2567–2573, 1996[CrossRef][Medline] 24. Poulsgard L, Ronne M, Schmidek HH : The cytogenetic and molecular genetic analysis of meningiomas, in Levine AJ, Schmidek HH (eds): Molecular Genetics of Nervous System Tumors. New York, NY, Wiley-Liss, 1993, pp 249–254 25. Rey JA, Bello MJ, de Campos JM, et al: Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches. Cancer Genet Cytogenet 66:1–10, 1993[CrossRef][Medline]
26. Seizinger BR, De La MS, Atkins L, et al: Molecular genetic approach to human meningioma: Loss of genes on chromosome 22. Proc Natl Acad Sci U S A 84:5419–5423, 1987 27. Vagner-Capodano AM, Grisoli F, Gambarelli D, et al: Correlation between cytogenetic and histopathological findings in 75 human meningiomas. Neurosurgery 32:892–900, 1993[Medline] 28. Zang KD: Cytological and cytogenetical studies on human meningioma. Cancer Genet Cytogenet 6:249–274, 1982[CrossRef][Medline] 29. Zang KD, Singer H: Chromosomal constitution of meningiomas. Nature 216:84–85, 1967[CrossRef][Medline] 30. Zankl H, Zang KD: Cytological and cytogenetical studies on brain tumors: 4. Identification of the missing G chromosome in human meningiomas as no. 22 by fluorescence technique. Humangenetik 14:167–169, 1972[CrossRef][Medline]
31. Weber RG, Bostrom J, Wolter M, et al: Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: Toward a genetic model of meningioma progression. Proc Natl Acad Sci U S A 94:14719–14724, 1997 32. Arnoldus EP, Wolters LB, Voormolen JH, et al: Interphase cytogenetics: A new tool for the study of genetic changes in brain tumors. J Neurosurg 76:997–1003, 1992[Medline] 33. Kasai H, Kawamoto K: Cytogenical analysis of brain tumors by FISH (fluorescence in situ hybridization) and FCM (flow cytometry). Noshuyo Byori 12:75–82, 1995[Medline] 34. Kim JH, Lee SH, Rhee CH, et al: Loss of heterozygosity on chromosome 22q and 17p correlates with aggressiveness of meningiomas. J Neurooncol 40:101–106, 1998[CrossRef][Medline] 35. Lamszus K, Kluwe L, Matschke J, et al: Allelic losses at 1p, 9q, 10q, 14q, and 22q in the progression of aggressive meningiomas and undifferentiated meningeal sarcomas. Cancer Genet Cytogenet 110:103–110, 1999[CrossRef][Medline] 36. Lindblom A, Ruttledge M, Collins VP, et al: Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression. Int J Cancer 56:354–357, 1994[Medline] 37. Ozaki S, Nishizaki T, Ito H, et al: Comparative genomic hybridization analysis of genetic alterations associated with malignant progression of meningioma. J Neurooncol 41:167–174, 1999[CrossRef][Medline] 38. Sanson M, Richard S, Delattre O, et al: Allelic loss on chromosome 22 correlates with histopathological predictors of recurrence of meningiomas. Int J Cancer 50:391–394, 1992[Medline] 39. Zattara-Cannoni H, Gambarelli D, Dufour H, et al: Contribution of cytogenetics and FISH in the diagnosis of meningiomas: A study of 189 tumors. Ann Genet 41:164–175, 1998[Medline] 40. Maillo A, Diaz P, Sayagues JM, et al: Gains of chromosome 22 by fluorescence in situ hybridization in the context of an hyperdiploid karyotype are associated with aggressive clinical features in meningioma patients. Cancer 92:377–385, 2001[CrossRef][Medline] 41. Simpson D: The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22–39, 1957[Medline] 42. García García J, Muñoz de la Espada JB, Orfao de Matos A, et al: Correlación clinico-biológica y características del ADN en 74 pacientes con cáncer colorrectal (citometría de flujo en piezas en fresco). Cir Esp 51:16–20, 1992 43. Paz-Bouza JI, Orfao A, Abad MM, et al: Transrectal fine needle aspiration biopsy of the prostate combining cytomorphologic, DNA status and cell cycle distribution studies. Pathol Res Pract 190:682–689, 1994[Medline] 44. Sayagués JM, Tabernero MD, Maillo A, et al: Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization (FISH) using 10 chromosome-specific probes. Cytometry 50:153–159, 2002[CrossRef][Medline] 45. Tabernero MD, San Miguel JF, García-Sanz R, et al: Incidence of chromosome numerical changes in multiple myeloma: Fluorescence in situ hybridization analysis using 15 chromosome-specific probes. Am J Pathol 149:153–161, 1996[Abstract] 46. Vindelov L, Christensen IJ, Nissen NI: A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3:323–327, 1983[CrossRef][Medline] 47. Lekanne Deprez RH, Riegman PH, van Drunen E, et al: Cytogenetic, molecular genetic and pathological analyses in 126 meningiomas. J Neuropathol Exp Neurol 54:224–235, 1995[Medline] 48. Bello MJ, de Campos JM, Vaquero J, et al: High-resolution analysis of chromosome arm 1p alterations in meningioma. Cancer Genet Cytogenet 120:30–36, 2000[CrossRef][Medline] 49. Cai DX, Banerjee R, Scheithauer BW, et al: Chromosome 1p and 14q FISH analysis in clinicopathologic subsets of meningioma: Diagnostic and prognostic implications. J Neuropathol Exp Neurol 60:628–636, 2001[Medline] 50. Ishino S, Hashimoto N, Fushiki S, et al: Loss of material from chromosome arm 1p during malignant progression of meningioma revealed by fluorescent in situ hybridization. Cancer 83:360–366, 1998[CrossRef][Medline] 51. Lopez-Gines C, Cerda-Nicolas M, Gil-Benso R, et al: Loss of 1p in recurrent meningiomas: A comparative study in successive recurrences by cytogenetics and fluorescence in situ hybridization. Cancer Genet Cytogenet 125:119–124, 2001[CrossRef][Medline]
52. Muller P, Henn W, Niedermayer I, et al: Deletion of chromosome 1p and loss of expression of alkaline phosphatase indicate progression of meningiomas. Clin Cancer Res 5:3569–3577, 1999 53. Sawyer JR, Husain M, Pravdenkova S, et al: A role for telomeric and centromeric instability in the progression of chromosome aberrations in meningioma patients. Cancer 88:440–453, 2000[CrossRef][Medline]
54. Simon M, von Deimling A, Larson JJ, et al: Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: A genetic model of meningioma progression. Cancer Res 55:4696–4701, 1995 55. Simon M, Kokkino AJ, Warnick RE, et al: Role of genomic instability in meningioma progression. Genes Chromosomes Cancer 16:265–269, 1996[CrossRef][Medline] 56. Lopez-Gines C, Cerda-Nicolas M, Barcia-Salorio JL, et al: Cytogenetical findings of recurrent meningiomas: A study of 10 tumors. Cancer Genet Cytogenet 85:113–117, 1995[CrossRef][Medline]
57. Rempel SA, Schwechheimer K, Davis RL, et al: Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression. Cancer Res 53:2386–2392, 1993 (10 suppl) 58. Cerda-Nicolas M, Lopez-Gines C, Perez-Bacete M, et al: Histopathological and cytogenetic findings in benign, atypical and anaplastic human meningiomas: A study of 60 tumors. Clin Neuropathol 19:259–267, 2000[Medline] 59. Menon AG, Rutter JL, von Sattel JP, et al: Frequent loss of chromosome 14 in atypical and malignant meningioma: Identification of a putative ‘tumor progression’ locus. Oncogene 14:611–616, 1997[CrossRef][Medline] 60. Schneider BF, Shashi V, Kap-herr C, et al: Loss of chromosomes 22 and 14 in the malignant progression of meningiomas: A comparative study of fluorescence in situ hybridization (FISH) and standard cytogenetic analysis. Cancer Genet Cytogenet 85:101–104, 1995[CrossRef][Medline] 61. Tse JY, Ng HK, Lau KM, et al: Loss of heterozygosity of chromosome 14q in low- and high-grade meningiomas. Hum Pathol 28:779–785, 1997[CrossRef][Medline] 62. Logan JA, Seizinger BR, Atkins L, et al: Loss of the Y chromosome in meningiomas: A molecular genetic approach. Cancer Genet Cytogenet 45:41–47, 1990[CrossRef][Medline] 63. Casalone R, Simi P, Granata P, et al: Correlation between cytogenetic and histopathological findings in 65 human meningiomas. Cancer Genet Cytogenet 45:237–243, 1990[CrossRef][Medline] 64. Ketter R, Henn W, Niedermayer I, et al: Predictive value of progression-associated chromosomal aberrations for the prognosis of meningiomas: A retrospective study of 198 cases. J Neurosurg 95:601–607, 2001[Medline] 65. Steudel WI, Feld R, Henn W, et al: Correlation between cytogenetic and clinical findings in 215 human meningiomas. Acta Neurochir (Wien) 65:73–76, 1996 (Suppl) Submitted July 25, 2002; accepted June 3, 2003. This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||
|
TOP
ABSTRACT
INTRODUCTION
dual-color probe; for chromosomes 11 and 14, LSI IgH/CCD1 dual-color probe; for chromosome X and Y, CEP X DNA probe, conjugated with Spectrum Orange and CEP Y DNA probe, conjugated with Spectrum Green; for chromosomes 1 and 10, Midisatellite 1p36 Probe direct labeled with fluorescein isothiocyanate (D1, Q-BIOgene) and the Spectrum Orange–labeled CEP 10 DNA probe for chromosome 10. Selection of the probes was based on the following criteria: specificity for a target chromosome and chromosome region that is known to be deleted frequently or gained in meningiomas; and quality of the probe as evaluated by its hybridization specificity, efficiency, and the fluorescence intensity of the hybridization signals obtained in normal diploid nuclei. 
2 test was applied to assess the statistical significance of differences observed between groups (cross-tab; SPSS) 
