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Automatized assessment of 1p36-19q13 status in gliomas by interphase FISH assay on touch imprints of frozen tumours

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Abstract

Molecular genetic analyses have demonstrated that combined losses in 1p36 and 19q13 were associated with a good response to treatment and a higher survival rates in oligodendrogliomas (O). The presence of such deletions in a subset of mixed oligoastrocytomas (OA) also suggests that 1p–19q status may assist the histological classification of gliomas. Representative frozen fragments of 25 patients with a primary grade II or III glioma [2 O, 8 astrocytic tumours (A), 15 OA] were selected and a sensitive interphase fluorescent in situ hybridization (FISH) analysis was developed on serial touch preparations using two sets of probes. A positive detection threshold at 6% was reached by the use of both touch imprints and a new set of LSI 1p36/19q13 Abbott-Vysis probes. Strong and discrete hybridization signals of these probes facilitated the following FISH analysis; indeed, an automatic analysis of the hybridization patterns (Metafer 4, Metasystems, Althlussheim, Germany) was compared with visual counting. Both methods were highly correlated and combined 1p–19q losses found in five tumours with an oligodendroglial component (2 O, 3 OA). The automatic system allowed the capture and storage of hybridization patterns and the processing of several slides. A convenient checking of the nuclei gallery was done with direct recall and visual verification on the slides of nuclei with ambiguous hybridization patterns. The recently developed probes together with automatic counting may facilitate multicentric evaluation and standardization of 1p–19q assessment in gliomas.

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References

  1. Ambros PF, Ambros IM (2001) Pathology and biology guidelines for resectable and unresectable neuroblastic tumors and bone marrow examination guidelines. Med Pediatr Oncol 37:492–504

    Article  PubMed  CAS  Google Scholar 

  2. Bailey P, Cushing H (1928) A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis. JB Lippincott, Philadelphia

    Google Scholar 

  3. Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M (2005) Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene. Clin Cancer Res 11:1119–1128

    PubMed  CAS  Google Scholar 

  4. Bauman GS, Cairncross JG (2001) Multidisciplinary management of adult anaplastic oligodendrogliomas and anaplastic mixed oligo-astrocytomas. Semin Radiat Oncol 11:170–180

    Article  PubMed  CAS  Google Scholar 

  5. Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY (2003) Primary brain tumours in adults. Lancet 361:323–331

    Article  PubMed  Google Scholar 

  6. Belaud-Rotureau MA, Parrens M, Dubus P, Garroste JC, de Mascarel A, Merlio JP (2002) A comparative analysis of FISH, RT-PCR, PCR, and immunohistochemistry for the diagnosis of mantle cell lymphomas. Mod Pathol 15:517–525

    Article  PubMed  Google Scholar 

  7. Belaud-Rotureau MA, Parrens M, Dubus P, Turmo M, Lacroute G, Taine L, Vago P, De Mascarel A, Merlio JP (2002) Interphase FISH analysis on histologic sections of fixed tissues for t(11;14) (q13;q32) detection in mantle cell lymphoma and t(8;14)(q24;q32) in Burkitt’s lymphoma. Ann Pathol 22:145–149

    PubMed  Google Scholar 

  8. Bello MJ, Leone PE, Vaquero J, de Campos JM, Kusak ME, Sarasa JL, Pestana A, Rey JA (1995) Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors. Int J Cancer 64:207–210

    Article  PubMed  CAS  Google Scholar 

  9. Bello MJ, Vaquero J, de Campos JM, Kusak ME, Sarasa JL, Saez-Castresana J, Pestana A, Rey JA (1994) Molecular analysis of chromosome 1 abnormalities in human gliomas reveals frequent loss of 1p in oligodendroglial tumors. Int J Cancer 57:172–175

    Article  PubMed  CAS  Google Scholar 

  10. Bouvier C, Roll P, Quilichini B, Metellus P, Calisti A, Gilles S, Chinot O, Fina F, Martin PM, Figarella-Branger D (2004) Deletions of chromosomes 1p and 19q are detectable on frozen smears of gliomas by FISH: usefulness for stereotactic biopsies. J Neurooncol 68:141–149

    Article  PubMed  Google Scholar 

  11. Buckner JC, Gesme D Jr, O’Fallon JR, Hammack JE, Stafford S, Brown PD, Hawkins R, Scheithauer BW, Erickson BJ, Levitt R, Shaw EG, Jenkins R (2003) Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol 21:251–255

    Article  PubMed  CAS  Google Scholar 

  12. Burger PC, Minn AY, Smith JS, Borell TJ, Jedlicka AE, Huntley BK, Goldthwaite PT, Jenkins RB, Feuerstein BG (2001) Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study of paraffin-embedded sections. Mod Pathol 14:842–853

    CAS  Google Scholar 

  13. Cairncross JG, Macdonald DR (1988) Successful chemotherapy for recurrent malignant oligodendroglioma. Ann Neurol 23:360–364

    Article  PubMed  CAS  Google Scholar 

  14. Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479

    Article  PubMed  CAS  Google Scholar 

  15. Chinot O (2001) Chemotherapy for the treatment of oligodendroglial tumors. Semin Oncol 28:13–18

    Article  PubMed  CAS  Google Scholar 

  16. Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK (1997) Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 79:1381–1393

    Article  PubMed  CAS  Google Scholar 

  17. Elia-Pasquet S, Provost D, Jaffre A, Loiseau H, Vital A, Kantor G, Maire JP, Dautheribes M, Darrouzet V, Dartigues JF, Brochard P, Baldi I (2004) Incidence of central nervous system tumors in Gironde, France. Neuroepidemiology 23:110–117

    Article  PubMed  Google Scholar 

  18. Fallon KB, Palmer CA, Roth KA, Nabors LB, Wang W, Carpenter M, Banerjee R, Forsyth P, Rich K, Perry A (2004) Prognostic value of 1p, 19q, 9p, 10q, and EGFR-FISH analyses in recurrent oligodendrogliomas. J Neuropathol Exp Neurol 63:314–322

    PubMed  CAS  Google Scholar 

  19. Felsberg J, Erkwoh A, Sabel MC, Kirsch L, Fimmers R, Blaschke B, Schlegel U, Schramm J, Wiestler OD, Reifenberger G (2004) Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival. Brain Pathol 14:121–130

    Article  PubMed  CAS  Google Scholar 

  20. Fuller CE, Schmidt RE, Roth KA, Burger PC, Scheithauer BW, Banerjee R, Trinkaus K, Lytle R, Perry A (2003) Clinical utility of fluorescence in situ hybridization (FISH) in morphologically ambiguous gliomas with hybrid oligodendroglial/astrocytic features. J Neuropathol Exp Neurol 62:1118–1128

    PubMed  Google Scholar 

  21. Gelpi E, Ambros IM, Birner P, Luegmayr A, Drlicek M, Fischer I, Kleinert R, Maier H, Huemer M, Gatterbauer B, Anton J, Rossler K, Budka H, Ambros PF, Hainfellner JA (2003) Fluorescent in situ hybridization on isolated tumor cell nuclei: a sensitive method for 1p and 19q deletion analysis in paraffin-embedded oligodendroglial tumor specimens. Mod Pathol 16:708–715

    Article  PubMed  Google Scholar 

  22. Giannini C, Scheithauer BW, Weaver AL, Burger PC, Kros JM, Mork S, Graeber MB, Bauserman S, Buckner JC, Burton J, Riepe R, Tazelaar HD, Nascimento AG, Crotty T, Keeney GL, Pernicone P, Altermatt H (2001) Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading. J Neuropathol Exp Neurol 60:248–262

    PubMed  CAS  Google Scholar 

  23. Hartmann C, Mueller W, Lass U, Kamel-Reid S, von Deimling A (2005) Molecular genetic analysis of oligodendroglial tumors. J Neuropathol Exp Neurol 64:10–14

    PubMed  CAS  Google Scholar 

  24. Hashimoto N, Murakami M, Takahashi Y, Fujimoto M, Inazawa J, Mineura K (2003) Correlation between genetic alteration and long-term clinical outcome of patients with oligodendroglial tumors, with identification of a consistent region of deletion on chromosome arm 1p. Cancer 97:2254–2261

    Article  PubMed  CAS  Google Scholar 

  25. Hatanpaa KJ, Burger PC, Eshleman JR, Murphy KM, Berg KD (2003) Molecular diagnosis of oligodendroglioma in paraffin sections. Lab Invest 83:419–428

    PubMed  CAS  Google Scholar 

  26. Ino Y, Betensky RA, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Ramsay DA, Cairncross JG, Louis DN (2001) Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7:839–845

    PubMed  CAS  Google Scholar 

  27. Iuchi T, Namba H, Iwadate Y, Shishikura T, Kageyama H, Nakamura Y, Ohira M, Yamaura A, Osato K, Sakiyama S, Nakagawara A (2002) Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors. Genes Chromosomes Cancer 35:170–175

    Article  PubMed  CAS  Google Scholar 

  28. Jenkins RB, Curran W, Scott CB, Cairncross G (2001) Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group. Am J Clin Oncol 24:506–508

    Article  PubMed  CAS  Google Scholar 

  29. Jeuken JW, Sprenger SH, Vermeer H, Kappelle AC, Boerman RH, Wesseling P (2002) Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about malignant progression detected using comparative genomic hybridization. J Neurosurg 96:559–564

    PubMed  Google Scholar 

  30. Kitange G, Misra A, Law M, Passe S, Kollmeyer TM, Maurer M, Ballman K, Feuerstein BG, Jenkins RB (2005) Chromosomal imbalances detected by array comparative genomic hybridization in human oligodendrogliomas and mixed oligoastrocytomas. Genes Chromosomes Cancer 42:68–77

    Article  PubMed  CAS  Google Scholar 

  31. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2000) The WHO classification of tumors of the nervous system; discussion 226–229. J Neuropathol Exp Neurol 61:215–225

    Google Scholar 

  32. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, Louis DN, Wiestler OD, von Deimling A (1995) Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 54:91–95

    PubMed  CAS  Google Scholar 

  33. Louis DN, Holland EC, Cairncross JG (2001) Glioma classification: a molecular reappraisal. Am J Pathol 159:779–786

    PubMed  CAS  Google Scholar 

  34. Macdonald DR, Gaspar LE, Cairncross JG (1990) Successful chemotherapy for newly diagnosed aggressive oligodendroglioma. Ann Neurol 27:573–574

    Article  PubMed  CAS  Google Scholar 

  35. McLendon RE, Rasheed BK, Wiltshire RN, Herndon J (2003) Correlation of 1p–19q-defects in human gliomas with the light microscopic appearance of oligodendroglioma. Mod Pathol 2004:604–605

    Google Scholar 

  36. Mittler MA, Walters BC, Stopa EG (1996) Observer reliability in histological grading of astrocytoma stereotactic biopsies. J Neurosurg 85:1091–1094

    Article  PubMed  CAS  Google Scholar 

  37. Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J, Veelken J, Schramm J, Weller M, Wiestler OD, Louis DN, von Deimling A (2002) Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 161:313–319

    PubMed  CAS  Google Scholar 

  38. Nigro JM, Misra A, Zhang L, Smirnov I, Colman H, Griffin C, Ozburn N, Chen M, Pan E, Koul D, Yung WK, Feuerstein BG, Aldape KD (2005) Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. Cancer Res 65:1678–1686

    Article  PubMed  CAS  Google Scholar 

  39. Perry A, Fuller CE, Banerjee R, Brat DJ, Scheithauer BW (2003) Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci 8:a1–a9

    Article  PubMed  CAS  Google Scholar 

  40. Perry JR, Louis DN, Cairncross JG (1999) Current treatment of oligodendrogliomas. Arch Neurol 56:434–436

    Article  PubMed  CAS  Google Scholar 

  41. Ransom DT, Ritland SR, Kimmel DW, Moertel CA, Dahl RJ, Scheithauer BW, Kelly PJ, Jenkins RB (1992) Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas. Genes Chromosomes Cancer 5:348–356

    Article  PubMed  CAS  Google Scholar 

  42. Ransom DT, Ritland SR, Moertel CA, Dahl RJ, O’Fallon JR, Scheithauer BW, Kimmel DW, Kelly PJ, Olopade OI, Diaz MO et al (1992) Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas. Genes Chromosomes Cancer 5:357–374

    Article  PubMed  CAS  Google Scholar 

  43. Reifenberger G, Louis DN (2003) Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 62:111–126

    PubMed  CAS  Google Scholar 

  44. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP (1994) Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 145:1175–1190

    PubMed  CAS  Google Scholar 

  45. Remstein ED, Kurtin PJ, Buno I, Bailey RJ, Proffitt J, Wyatt WA, Hanson CA, Dewald GW (2000) Diagnostic utility of fluorescence in situ hybridization in mantle-cell lymphoma. Br J Haematol 110:856–862

    Article  PubMed  CAS  Google Scholar 

  46. Rey JA, Bello MJ, de Campos JM, Kusak ME, Moreno S (1987) Chromosomal composition of a series of 22 human low-grade gliomas. Cancer Genet Cytogenet 29:223–237

    Article  PubMed  CAS  Google Scholar 

  47. Rubio MP, Correa KM, Ueki K, Mohrenweiser HW, Gusella JF, von Deimling A, Louis DN (1994) The putative glioma tumor suppressor gene on chromosome 19q maps between APOC2 and HRC. Cancer Res 54:4760–4763

    PubMed  CAS  Google Scholar 

  48. Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, Hosek SM, Kimmel D, O’Fallon J, Yates A, Feuerstein BG, Burger PC, Scheithauer BW, Jenkins RB (1999) Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18:4144–152

    Article  PubMed  CAS  Google Scholar 

  49. Smith JS, Jenkins RB (2000) Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications. Front Biosci 5:D213–D231

    Article  PubMed  CAS  Google Scholar 

  50. Smith JS, Perry A, Borell TJ, Lee HK, O’Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    PubMed  CAS  Google Scholar 

  51. van den Bent MJ (2001) New perspectives for the diagnosis and treatment of oligodendroglioma. Expert Rev Anticancer Ther 1:348–356

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by grants from the region aquitaine and the ligue contre le Cancer (Comité de la Gironde). The authors thank Michelle Turmo for her technical support. The experiments comply with current laws of the European countries

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Correspondence to Jean-Philippe Merlio.

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Belaud-Rotureau, MA., Meunier, N., Eimer, S. et al. Automatized assessment of 1p36-19q13 status in gliomas by interphase FISH assay on touch imprints of frozen tumours. Acta Neuropathol 111, 255–263 (2006). https://doi.org/10.1007/s00401-005-0001-4

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