Top

Published in:

01-01-2005 | Review

Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence

Authors: Christian H. Rickert, Werner Paulus

Published in: Acta Neuropathologica | Issue 1/2005

Abstract

Brain tumors account for approximately 20% of all childhood cancers, and are the leading cause of cancer morbidity and mortality among children. Although numerous demographic, clinical and therapeutic parameters have been identified over the past few years that have significant prognostic bearing for some pediatric brain tumors, predicting the clinical course and outcome among children with central nervous system tumors is still difficult. A survey of publications on prognosis-related histopathological and immunohistochemical features among pediatric brain tumors revealed 172 series, of which 91 presented statistically significant outcome-associated parameters as defined by a P value of less than 0.05. Most investigations revealing significant prognosis-related markers were performed on medulloblastomas (30 publications), ependymomas (25) and astrocytic tumors (18). In total, 16 cohorts consisted of more than 100 cases (5 on ependymomas, 3 each on medulloblastomas and astrocytic tumors). On the other hand, there were also 13 series with fewer than 20 cases (5 on medulloblastomas). Potentially prognostic histopathological markers vary among different entities and consist of assessment of necroses, mitoses, differentiation, vascular proliferation, and growth pattern, whereas immunohistochemical features include proliferation markers (Ki-67, MIB-1), expression of oncogenes/tumor suppressor genes and their proteins (TP53, c-erbB2), growth factor and hormonal receptors (VEGF, EGFR, HER2, HER4, ErbB-2), cell cycle genes (p27, p14ARF) and cell adhesion molecules, as well as factors potentially related to therapeutic resistance (DNA topoisomerase IIalpha, metallothionein, P-glycoprotein, tenascin). This review discusses the prognostic potential of histopathological and immunohistochemical markers that can be investigated by the practicing neuropathologist as part of the routine diagnostic workload, and scrutinizes their benefit for predicting therapy response and patient outcome among children with brain tumors.

Adamson TE, Wiestler OD, Kleihues P, Yasargil MG (1990) Correlation of clinical and pathological features in surgically treated craniopharygiomas. J Neurosurg 73:12–17

Adesina AM, Dunn ST, Moore WE, Nalbantoglu J (2000) Expression of p27kip1 and p53 in medulloblastoma: relationship with cell proliferation and survival. Pathol Res Pract 196:243–250PubMed

Asai A, Hoshino T, Edwards MS, Davis RL (1992) Predicting the recurrence of ependymomas from the bromodeoxyuridine labeling index. Childs Nerv Syst 8:273–278CrossRefPubMed

Bennetto L, Foreman N, Harding B, Hayward R, Ironside J, Love S, Ellison D (1998) Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas. Neuropathol Appl Neurobiol 24:434–440CrossRefPubMed

Bernhardtsen T, Laursen H, Bojsen-Moller M, Gjerris F (2003) Sub-classification of low-grade cerebellar astrocytoma: is it clinically meaningful? Childs Nerv Syst 19:729–735CrossRefPubMed

Biegel JA, Janss AJ, Raffel C, Sutton L, Rorke LB, Harper JM, Phillips PC (1997) Prognostic significance of chromosome 17p deletions in childhood primitive neuroectodermal tumors (medulloblastomas) of the central nervous system. Clin Cancer Res 3:473–478PubMed

Blümcke I, Luyken C, Urbach H, Schramm J, Wiestler OD (2004) An isomorphic subtype of long-term epilepsy-associated astrocytomas associated with benign prognosis. Acta Neuropathol 107:381–388CrossRefPubMed

Bonnin JM, Rubinstein LJ (1989) Astroblastomas: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients. Neurosurgery 25:6–13

Bouffet E, Perilongo G, Canete A, Massimino M (1998) Intracranial ependymomas in children: a critical review of prognostic factors and a plea for cooperation. Med Pediatr Oncol 30:319–329

10.

Bowers DC, Gargan L, Kapur P, Reisch JS, Mulne AF, Shapiro KN, Elterman RD, Winick NJ, Margraf LR (2003) Study of the MIB-1 labeling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents. J Clin Oncol 21:2968–2973CrossRefPubMed

11.

Brat DJ, Hirose Y, Cohen KJ, Feuerstein BG, Burger PC (2000) Astroblastoma: clinicopathologic features and chromosomal abnormalities defined by comparative genomic hybridization. Brain Pathol 10:342–352PubMed

12.

Bredel M, Pollack IF, Campbell JW, Hamilton RL (1997) Basic fibroblast growth factor expression as a predictor of prognosis in pediatric high-grade gliomas. Clin Cancer Res 3:2157–2164PubMed

13.

Bredel M, Pollack IF, Hamilton RL, Birner P, Hainfellner JA, Zentner J (2002) DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas. Int J Cancer 99:817–820CrossRefPubMed

14.

Bredel M, Slavc I, Birner P, Czech T, Haberler C, Strobel T, Wolfsberger S, Budka H, Hainfellner JA (2002) DNA topoisomerase IIalpha expression in optic pathway gliomas of childhood. Eur J Cancer 38:393–400CrossRefPubMed

15.

Brown HG, Kepner JL, Perlman EJ, Friedman HS, Strother DR, Duffner PK, Kun LE, Goldthwaite PT, Burger PC (2000) “Large cell/anaplastic” medulloblastomas: a Pediatric Oncology Group Study. J Neuropathol Exp Neurol 59:857–865PubMed

16.

Burnstine MA, Levin LA, Louis DN, Hedley-Whyte ET, Kupsky WJ, Doepner D, Albert DM (1993) Nucleolar organizer regions in optic gliomas. Brain 116:1465–1476PubMed

17.

Caputy AJ, McCullough DC, Manz HJ, Patterson K, Hammock MK (1987) A review of the factors influencing the prognosis of medulloblastoma. The importance of cell differentiation. J Neurosurg 66:80–87

18.

Carlotti CG, Salhia B, Weitzman S, Greenberg M, Dirks PB, Mason W, Becker LE, Rutka JT (2002) Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children. Acta Neuropathol 103:1–10

19.

Carter M, Nicholson J, Ross F, Crolla J, Allibone R, Balaji V, Perry R, Walker D, Gilbertson R, Ellison D (2002) Genetic abnormalities detected in ependymomas by comparative genomic hybridisation. Br J Cancer 86:929–939CrossRefPubMed

20.

Chintagumpala MM, Armstrong D, Miki S, Nelson T, Cheek W, Laurent J, Woo SY, Mahoney DH Jr (1996) Mixed neuronal-glial tumors (gangliogliomas) in children. Pediatr Neurosurg 24:306–313PubMed

21.

Coffin CM, Braun JT, Wick MR, Dehner LP (1990) A clinicopathologic and immunohistochemical analysis of 53 cases of medulloblastoma with emphasis on synaptophysin expression. Mod Pathol 3:164–170PubMed

22.

Czerwionka M, Korf HW, Hoffmann O, Busch H, Schachenmayr W (1989) Differentiation in medulloblastomas: correlation between the immunocytochemical demonstration of photoreceptor markers (S-antigen, rhodopsin) and the survival rate in 66 patients. Acta Neuropathol 78:629–636PubMed

23.

Dearnaley DP, A’Hern RP, Whittaker S, Bloom HJ (1990) Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962–1987. Int J Radiat Oncol Biol Phys 18:773–781PubMed

24.

Dirven CM, Koudstaal J, Mooij JJ, Molenaar WM (1998) The proliferative potential of the pilocytic astrocytoma: the relation between MIB-1 labeling and clinical and neuro-radiological follow-up. J Neurooncol 37:9–16CrossRefPubMed

25.

Dirven CM, Koudstaal J, Mooij JA, Molenaar WM (1999) AgNOR staining may reflect the growth potential of pilocytic astrocytomas. Childs Nerv Syst 15:384–388CrossRefPubMed

26.

Drach LM, Kammermeier M, Neirich U, Jacobi G, Kornhuber B, Lorenz R, Schlote W (1996) Accumulation of nuclear p53 protein and prognosis of astrocytomas in childhood and adolescence. Clin Neuropathol 15:67–73PubMed

27.

Duo D, Gasverde S, Benech F, Zenga F, Giordana MT (2003) MIB-1 immunoreactivity in craniopharyngiomas: a clinico-pathological analysis. Clin Neuropathol 22:229–234PubMed

28.

Eberhart CG, Kepner JL, Goldthwaite P, Kun LE, Duffner PK, Friedman HS, Strother DR, Burger PC (2002) Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer 94:552–560CrossRefPubMed

29.

Eberhart CG, Kratz JE, Wang Y, Summers K, Stearns D, Cohen K, Dang CV, Burger PC (2004) Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol 63:441–449PubMed

30.

Ellison D (2002) Classifying the medulloblastoma: insights from morphology and molecular genetics. Neuropathol Appl Neurobiol 28:257–282CrossRefPubMed

31.

Ernestus RI, Wilcke O, Schroder R (1989) Intracranial ependymomas: prognostic aspects. Neurosurg Rev 12:157–163

32.

Ernestus RI, Schröder R, Stutzer H, Klug N (1996) Prognostic relevance of localization and grading in intracranial ependymomas of childhood. Child’s Nerv Syst 12:522–526

33.

Ernestus RI, Schröder R, Stutzer H, Klug N (1997) The clinical and prognostic relevance of grading in intracranial ependymomas. Br J Neurosurg 11:421–428CrossRefPubMed

34.

Fauchon F, Jouvet A, Paquis P, Saint-Pierre G, Mottolese C, Ben Hassel M, Chauveinc L, Sichez JP, Philippon J, Schlienger M, Bouffet E (2000) Parenchymal pineal tumors: a clinicopathological study of 76 cases. Int J Radiat Oncol Biol Phys 46:959–968CrossRefPubMed

35.

Fernandez C, Figarella-Branger D, Girard N, Bouvier-Labit C, Gouvernet J, Paz Paredes A, Lena G (2003) Pilocytic astrocytomas in children: prognostic factors—a retrospective study of 80 cases. Neurosurgery 53:544–553

36.

Figarella-Branger D, Gambarelli D, Dollo C, Devictor B, Perez-Castillo AM, Genitori L, Lena G, Choux M, Pellissier JF (1991) Infratentorial ependymomas of childhood. Correlation between histological features, immunohistological phenotype, silver nucleolar organizer region staining values and post-operative survival in 16 cases. Acta Neuropathol 82:208–216CrossRefPubMed

37.

Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC, Lena G, Choux M, Pellissier JF (2000) Prognostic factors in intracranial ependymomas in children. J Neurosurg 93:605–613

38.

Fisher BJ, Naumova E, Leighton CC, Naumov GN, Kerklviet N, Fortin D, Macdonald DR, Cairncross JG, Bauman GS, Stitt L (2002) Ki-67: a prognostic factor for low-grade glioma? Int J Radiat Oncol Biol Phys 52:996–1001CrossRefPubMed

39.

Foreman NK, Love S, Thorne R (1996) Intracranial ependymomas: analysis of prognostic factors in a population-based series. Pediatr Neurosurg 24:119–125

40.

Fouladi M, Helton K, Dalton J, Gilger E, Gajjar A, Merchant T, Kun L, Newsham I, Burger P, Fuller C (2003) Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients. Cancer 98:2232–2244CrossRefPubMed

41.

Gaffney CC, Sloane JP, Bradley NJ, Bloom HJ (1985) Primitive neuroectodermal tumours of the cerebrum. Pathology and treatment. J Neurooncol 3:23–33

42.

Gajjar A, Hernan R, Kocak M, Fuller C, Lee Y, McKinnon PJ, Wallace D, Lau C, Chintagumpala M, Ashley DM, Kellie SJ, Kun L, Gilbertson RJ (2004) Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 22:984–993CrossRefPubMed

43.

Gerszten PC, Pollack IF, Martinez AJ, Lo KH, Janosky J, Albright AL (1996) Intracranial ependymomas of childhood. Lack of correlation of histopathology and clinical outcome. Pathol Res Pract 192:515–522PubMed

44.

Giangaspero F, Rigobello L, Badiali M, Loda M, Andreini L, Basso G, Zorzi F, Montaldi A (1992) Large-cell medulloblastomas. A distinct variant with highly aggressive behavior. Am J Surg Pathol 16:687–693

45.

Giangaspero F, Perilongo G, Fondelli MP, Brisigotti M, Carollo C, Burnelli R, Burger PC, Garre ML (1999) Medulloblastoma with extensive nodularity: a variant with favorable prognosis. J Neurosurg 91:971–977

46.

Giannini C, Scheithauer BW, Burger PC, Brat DJ, Wollan PC, Lach B, O’Neill BP (1999) Pleomorphic xanthoastrocytoma: what do we really know about it? Cancer 85:2033–2045PubMed

47.

Giannini C, Scheithauer BW, Burger PC, Christensen MR, Wollan PC, Sebo TJ, Forsyth PA, Hayostek CJ (1999) Cellular proliferation in pilocytic and diffuse astrocytomas. J Neuropathol Exp Neurol 58:46–53PubMed

48.

Gilbertson RJ, Pearson AD, Perry RH, Jaros E, Kelly PJ (1995) Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. Br J Cancer 71:473–477PubMed

49.

Gilbertson RJ, Jaros E, Perry RH, Kelly PJ, Lunec J, Pearson ADJ (1997) Mitotic percentage index: a new prognostic factor for childhood medulloblastoma. Eur J Cancer 33:609–615CrossRefPubMed

50.

Gilbertson RJ, Perry RH, Kelly PJ, Pearson AD, Lunec J (1997) Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Res 57:3272–3280PubMed

51.

Gilbertson RJ, Clifford SC, MacMeekin W, Meekin W, Wright C, Perry RH, Kelly P, Pearson AD, Lunec J (1998) Expression of the ErbB-neuregulin signaling network during human cerebellar development: implications for the biology of medulloblastoma. Cancer Res 58:3932–3941PubMed

52.

Gilbertson R, Wickramasinghe C, Hernan R, Balaji V, Hunt D, Jones-Wallace D, Crolla J, Perry R, Lunec J, Pearson A, Ellison D (2001) Clinical and molecular stratification of disease risk in medulloblastoma. Br J Cancer 85:705–712CrossRefPubMed

53.

Goldberg-Stern H, Gadoth N, Stern S, Cohen IJ, Zaizov R, Sandbank U (1991) The prognostic significance of glial fibrillary acidic protein staining in medulloblastoma. Cancer 68:568–573PubMed

54.

Goldwein JW, Glauser TA, Packer RJ, Finlay JL, Sutton LN, Curran WJ, Laehy JM, Rorke LB, Schut L, D’Angio GJ (1990) Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors. Cancer 66:557–563PubMed

55.

Grotzer MA, Janss AJ, Fung K, Biegel JA, Sutton LN, Rorke LB, Zhao H, Cnaan A, Phillips PC, Lee VM, Trojanowski JQ (2000) TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J Clin Oncol 18:1027–1035PubMed

56.

Grotzer MA, Geoerger B, Janss AJ, Zhao H, Rorke LB, Phillips PC (2001) Prognostic significance of Ki-67 (MIB-1) proliferation index in childhood primitive neuroectodermal tumors of the central nervous system. Med Pediatr Oncol 36:268–273

57.

Grotzer MA, Janss AJ, Fung KM, Sutton LN, Zhao H, Trojanowski JQ, Rorke LB, Phillips PC (2001) Abundance of apoptotic neoplastic cells in diagnostic biopsy samples is not a prognostic factor in childhood primitive neuroectodermal tumors of the central nervous system. J Pediatr Hematol Oncol 23:25–29

58.

Haapasalo H, Sallinen S, Sallinen P, Helen P, Jääskeläinen J, Salmi TT, Paetau A, Paljärvi L, Visakorpi T, Kalimo H (1999) Clinicopathological correlation of cell proliferation, apoptosis and p53 in cerebellar pilocytic astrocytomas. Neuropathol Appl Neurobiol 25:134–142CrossRefPubMed

59.

Hall PA, Going JJ (1999) Predicting the future: a critical appraisal of cancer prognosis studies. Histopathology 35:489–494CrossRefPubMed

60.

Hamilton RL, Pollack IF (1997) The molecular biology of ependymomas. Brain Pathol 7:807–822PubMed

61.

Haslam RH, Lamborn KR, Becker LE, Israel MA (1998) Tumor cell apoptosis present at diagnosis may predict treatment outcome for patients with medulloblastoma. J Pediatr Hematol Oncol 20:520–527

62.

Hayostek CJ, Shaw EG, Scheithauer B, O’Fallon JR, Weiland TL, Schomberg PJ, Kelly PJ, Hu TC (1993) Astrocytomas of the cerebellum. A comparative clinicopathologic study of pilocytic and diffuse astrocytomas. Cancer 72:856–869PubMed

63.

Heck K, Pyle P, Bruner JM (1994) Bcl-2 expression in cerebellar medulloblastomas. Brain Pathol 4:430

64.

Herms JW, Behnke J, Bergmann M, Christen HJ, Kolb R, Wilkening M, Markakis E, Hanefeld F, Kretzschmar HA (1997) Potential prognostic value of C-erbB-2 expression in medulloblastomas in very young children. J Pediatr Hematol Oncol 19:510–515

65.

Herms J, Neidt I, Lüscher I, Sommer A, Schürmann P, Schröder T, Bergmann M, Wilken B, Probst-Cousin S, Hernaiz-Driever P, Behnke J, Hansfeld F, Pietsch T, Kretschmar HA (2000) C-myc expression in medulloblastoma and its prognostic value. Int J Cancer 89:395–402CrossRefPubMed

66.

Hirose T, Scheithauer BW, Lopes MBS, Gerber HA, Altermatt HJ, VandenBerg SR (1997) Ganglioglioma: an ultrastructural and immunohistochemical study. Cancer 79:989–1003PubMed

67.

Ho DM, Wong TT, Liu HC (1991) Choroid plexus tumors in childhood. Histopathologic study and clinico-pathological correlation. Childs Nerv Syst 7:437–441PubMed

68.

Ho DM, Wong TT, Hsu CY, Ting LT, Chiang H (1998) MIB-1 labeling index in non-pilocytic astrocytoma of childhood. Cancer 82:2459–2466CrossRefPubMed

69.

Ho DM, Hsu CY, Wong TT, Chiang H (2001) A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma. J Neurooncol 54:77–85CrossRefPubMed

70.

Horn B, Heideman R, Geyer R, Pollack I, Packer R, Goldwein J, Tomita T, Schomberg P, Ater J, Luchtman-Jones L, Rivlin K, Lamborn K, Prados M, Bollen A, Berger M, Dahl G, McNeil E, Patterson K, Shaw D, Kubalik M, Russo C (1999) A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 21:203–211CrossRefPubMed

71.

Ilgren EB, Stiller CA, Hughes JT, Silberman D, Steckel N, Kaye A (1984) Ependymomas: a clinical and pathologic study. Part II. Survival features. Clin Neuropathol 3:122–127PubMed

72.

Ito S, Hoshino T, Prados MD, Edwards MS (1992) Cell kinetics of medulloblastomas. Cancer 70:671–678PubMed

73.

Ito S, Hoshino T, Shibuya M, Prados MD, Edwards MS, Davis RL (1992) Proliferative characteristics of juvenile pilocytic astrocytomas determined by bromodeoxyuridine labeling. Neurosurgery 31:413–418

74.

Jaing TH, Wang HS, Hung IJ, Tseng CK, Yang CP, Hung PC, Lui TN (2002) Intracranial germ cell tumors: a retrospective study of 44 children. Pediatr Neurol 26:369–373

75.

Jakacki RI (1999) Pineal and nonpineal supratentorial primitive neuroectodermal tumors. Childs Nerv Syst 15:586–591CrossRefPubMed

76.

Janss AJ, Yachnis AT, Silber JH, Trojanowski JQ, Lee VM, Sutton LN, Perilongo G, Rorke LB, Phillips PC (1996) Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors. Ann Neurol 39:481–489PubMed

77.

Jaros E, Lunec J, Perry RH, Kelly PJ, Pearson AD (1993) p53 protein overexpression identifies a group of central primitive neuroectodermal tumours with poor prognosis. Br J Cancer 68:801–807PubMed

78.

Jouvet A, Saint-Pierre G, Fauchon F, Privat K, Bouffet E, Ruchoux MM, Chauveinc L, Fevre-Montange M (2000) Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases. Brain Pathol 10:49–60PubMed

79.

Kaatsch P, Rickert CH, Kühl J, Schüz J, Michaelis J (2001) Population-based epidemiologal data of brain tumors in German children. Cancer 92:3155–3164CrossRefPubMed

80.

Kato T, Fujita M, Sawamura Y, Tada M, Abe H, Nagashima K, Nakamura N (1996) Clinicopathological study of choroid plexus tumors: immunohistochemical features and evaluation of proliferative potential by PCNA and Ki-67 immunostaining. Noshuyo Byori 13:99–105PubMed

81.

Klein R, Mölenkamp G, Sörensen N, Roggendorf W (1998) Favorable outcome of giant cell glioblastoma in a child. Report of an 11-year survival period. Childs Nerv Syst 14:288–291CrossRefPubMed

82.

Komotar RJ, Burger PC, Carson BS, Brem H, Olivi A, Goldthwaite PT, Tihan T (2004) Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery 54:72–79

83.

Kopelson G, Linggood RM, Kleinman GM (1983) Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management. Cancer 51:312–319PubMed

84.

Korshunov A, Golanov A, Ozerov S, Sycheva R (1999) Prognostic value of tumor-associated antigens immunoreactivity and apoptosis in medulloblastomas. An analysis of 73 cases. Brain Tumor Pathol 16:37–44PubMed

85.

Korshunov A, Sycheva R, Timirgaz V, Golanov A (1999) Prognostic value of immunoexpression of the chemoresistance-related proteins in ependymomas: an analysis of 76 cases. J Neurooncol 45:219–227CrossRefPubMed

86.

Korshunov A, Golanov A, Timirgaz V (2000) Immunohistochemical markers for intracranial ependymoma recurrence. An analysis of 88 cases. J Neurol Sci 177:72–82CrossRefPubMed

87.

Korshunov A, Golanov A, Timirgaz V (2001) p14ARF protein (FL-132) immunoreactivity in intracranial ependymomas and its prognostic significance: an analysis of 103 cases. Acta Neuropathol 102:271–277PubMed

88.

Korshunov A, Savostikova M, Ozerov S (2002) Immunohistochemical markers for prognosis of average-risk pediatric medulloblastomas. The effect of apoptotic index, TrkC, and c-myc expression. J Neurooncol 58:271–279CrossRefPubMed

89.

Korshunov A, Golanov A, Sycheva R, Timirgaz V (2004) The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients. Cancer 100:1230–1237CrossRefPubMed

90.

Kotylo PK, Robertson PB, Fineberg NS, Azzarelli B, Jakacki R (1997) Flow cytometric DNA analysis of pediatric intracranial ependymomas. Arch Pathol Lab Med 121:1255–1258PubMed

91.

Kovalic JJ, Flaris N, Grigsby PW, Pirkowski M, Simpson JR, Roth KA (1993) Intracranial ependymoma long term outcome, patterns of failure. J Neurooncol 15:125–131PubMed

92.

Kunishio K, Matsumoto K, Furuta T, Ohmoto T (1999) A clinical analysis of patients with primary intracranial germinomas: the relationship between proliferative potential and recurrence. No Shinkei Geka 27:127–132PubMed

93.

Lang FF, Epstein FJ, Ransohoff J, Allen JC, Wisoff J, Abbott IR, Miller DC (1993) Central nervous system gangliogliomas. Part 2: Clinical outcome. J Neurosurg 79:867–873

94.

Li VW, Folkerth RD, Watanabe H, Yu C, Rupnick M, Barnes P, Scott RM, Black PM, Sallan SE, Folkman J (1994) Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumours. Lancet 344:82–86CrossRefPubMed

95.

Losa M, Vimercati A, Acerno S, Barzaghi RL, Mortini P, Mangili F, Terreni MR, Santambrogio G, Giovanelli M (2004) Correlation between clinical characteristics and proliferative activity in patients with craniopharyngioma. J Neurol Neurosurg Psychiatry 75:889–892CrossRefPubMed

96.

Lutterbach J, Fauchon F, Schild SE, Chang SM, Pagenstecher A, Volk B, Ostertag C, Momm F, Jouvet A (2002) Malignant pineal parenchymal tumors in adult patients: patterns of care and prognostic factors. Neurosurgery 51:44–55

97.

Macaulay RJ, Jay V, Hoffman HJ, Becker LE (1993) Increased mitotic activity as a negative prognostic indicator in pleomorphic xanthoastrocytoma. Case report. J Neurosurg 79:761–768

98.

Machen SK, Prayson RA (1998) Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases. Hum Pathol 29:1511–1516CrossRefPubMed

99.

Maire JP, Guerin J, Rivel J, San Galli F, Bernard C, Dautheribes M, Caudry M (1992) Medulloblastoma in children. Prognostic incidence of vascular hyperplasia, coagulation necrosis and postoperative clinical state on survival. Neurochirurgie 38:80–88PubMed

100.

Maraziotis T, Perentes E, Karamitopoulou E, Nakagawa Y, Gessaga EC, Probst A, Frankfurter A (1992) Neuron-associated class III beta-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases. Acta Neuropathol 84:355–363CrossRefPubMed

101.

Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86:446–455

102.

McGirr SJ, Ebersold MJ, Scheithauer BW, Quast LM, Shaw EG (1988) Choroid plexus papillomas: long-term follow-up results in a surgically treated series. J Neurosurg. 69:843–849

103.

McManamy CS, Lamont JM, Taylor RE, Cole M, Pearson AD, Clifford SC, Ellison DW, United Kingdom Children’s Cancer Study Group (2003) Morphophenotypic variation predicts clinical behavior in childhood non-desmoplastic medulloblastomas. J Neuropathol Exp Neurol 62:627–632PubMed

104.

Mena H, Rushing EJ, Ribas JL, Delahunt B, McCarthy WF (1995) Tumors of the pineal parenchymal cells: a correlation of histological features, including nucleolar organizer regions, with survival in 35 cases. Hum Pathol 26:20–30CrossRefPubMed

105.

Merchant TE, Jenkins JJ, Burger PC, Sanford RA, Sherwood SH, Jones-Wallace D, Heideman RL, Thompson SJ, Helton KJ, Kun LE (2002) Influence of tumor grade on time to progression after irradiation for localized ependymoma in children. Int J Radiat Oncol Biol Phys 53:52–57CrossRefPubMed

106.

Miralbell R, Tolnay M, Bieri S, Probst A, Sappino AP, Berchtold W, Pepper MS, Pizzolato G (1999) Pediatric medulloblastoma: prognostic value of p53, bcl-2, Mib-1, and microvessel density. J Neurooncol 45:103–110CrossRefPubMed

107.

Nam DH, Wang KC, Kim YM, Chi JG, Kim SK, Cho BK (2000) The effect of isochromosome 17q presence, proliferative and apoptotic indices, expression of c-erbB-2, bcl-2 and p53 proteins on the prognosis of medulloblastoma. J Korean Med Sci 15:452–456PubMed

108.

Nicholson JC, Ross FM, Kohler JA, Ellison DW (1999) Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours. Br J Cancer 80:1322–1331CrossRefPubMed

109.

Nishi T, Kuratsu J, Takeshima H, Saito Y, Kochi M, Ushio Y (1999) Prognostic significance of the MIB-1 labeling index for patient with craniopharyngioma. Int J Mol Med 3:157–161PubMed

110.

Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J, Shikama N, Saeki N, Yoshii Y, Murayama S (2003) Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. Cancer 98:369–376CrossRefPubMed

111.

Orr LC, Fleitz J, McGavran L, Wyatt-Ashmead J, Handler M, Foreman NK (2002) Cytogenetics in pediatric low-grade astrocytomas. Med Pediatr Oncol 38:173–177

112.

Packer RJ, Sutton LN, Rorke LB, Littman PA, Sposto R, Rosenstock JG, Bruce DA, Schut L (1984) Prognostic importance of cellular differentiation in medulloblastoma of childhood. J Neurosurg 61:296–301

113.

Pahapill PA, Ramsay DA, Del Maestro RF (1996) Pleomorphic xanthoastrocytoma: case report and analysis of the literature concerning the efficacy of resection and the significance of necrosis. Neurosurgery 38:822–828

114.

Palma L, Russo A, Celli P (1984) Prognosis of the so-called “diffuse” cerebellar astrocytoma. Neurosurgery 15:315–317

115.

Papadopoulos DP, Giri S, Evans RG (1990) Prognostic factors and management of intracranial ependymomas. Anticancer Res 10:689–692PubMed

116.

Patt S, Giraldo M, Martin H (1994) AgNOR- and PCNA-studies in astrocytomas of the optic nerve. Zentralbl Pathol 140:83–87PubMed

117.

Paulus W, Jänisch W (1990) Clinico-pathologic correlations in epithelial choroid plexus neoplasms: a study of 52 cases. Acta Neuropathol 80:635–641CrossRefPubMed

118.

Paulus W, Honegger J, Keyvani K, Fahlbusch R (1999) Xanthogranuloma of the sellar region: a clinicopathological entity different from adamantinomatous craniopharyngioma. Acta Neuropathol 97:377–382CrossRefPubMed

119.

Pelc K, Vincent S, Ruchoux MM, Kiss R, Pochet R, Sariban E, Decaestecker C, Heizmann CW (2002) Calbindin-D(28k): a marker of recurrence for medulloblastomas. Cancer 95:410–419CrossRefPubMed

120.

Pencalet P, Maixner W, Sainte-Rose C, Lellouch-Tubiana A, Cinalli G, Zerah M, Pierre-Kahn A, Hoppe-Hirsch E, Bourgeois M, Renier D (1999) Benign cerebellar astrocytomas in children. J Neurosurg 90:265–273

121.

Perilongo G, Massimino M, Sotti G, Belfontali T, Masiero L, Rigobello L, Garre L, Carli M, Lombardi F, Solero C, Sainati L, Canale V, Prever AB del, Giangaspero F, Andreussi L, Mazza C, Madon E (1997) Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neurooncology Group. Med Pediatr Oncol 29:79–85CrossRefPubMed

122.

Pollack IF, Gerzten PC, Martinez AJ, Lo KH, Shultz B, Albright AL, Janosky J, Deutsch M (1995) Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 37:655–667

123.

Pollack IF, Campbell JW, Hamilton RL, Martinez AJ, Bozik ME (1997) Proliferation index as a predictor of prognosis in malignant gliomas of childhood. Cancer 79:849–856PubMed

124.

Pollack IF, Finkelstein SD, Woods J, Burnham J, Holmes EJ, Hamilton RL, Yates AJ, Boyett JM, Finlay JL, Sposto R, The Children’s Cancer Group (2002) Expression of p53 and prognosis in children with malignant gliomas. N Eng J Med 346:420–427CrossRef

125.

Pollack IF, Hamilton RL, Burnham J, Holmes EJ, Finkelstein SD, Sposto R, Yates AJ, Boyett JM, Finlay JL (2002) Impact of proliferation index on outcome in childhood malignant gliomas: results in a multi-institutional cohort. Neurosurgery 50:1238–1244

126.

Prados MD, Krouwer HG, Edwards MS, Cogen PH, Davis RL, Hoshino T (1992) Proliferative potential and outcome in pediatric astrocytic tumors. J Neurooncol 13:277–282CrossRefPubMed

127.

Prayson RA (1998) Cyclin D1 and MIB-1 immunohistochemistry in ependymomas: a study of 41 cases. Am J Clin Pathol 110:629–634PubMed

128.

Prayson RA, Khajavi K, Comair YG (1995) Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors. J Neuropathol Exp Neurol 54:513–520PubMed

129.

Qualman SJ, Shannon BT, Boesel CP, Jacobs D, Jinkens C, Hayes J (1992) Ploidy analysis and cerebrospinal fluid nephelometry as measures of clinical outcome in childhood choroid plexus neoplasia. Pathol Annu 27:305–321PubMed

130.

Rades D, Schild SE, Fehlauer F (2004) Prognostic value of the MIB-1 labeling index for central neurocytomas. Neurology 62:987–989PubMed

131.

Rawlings CE 3rd, Giangaspero F, Burger PC, Bullard DE (1988) Ependymomas: a clinicopathologic study. Surg Neurol 29:271–281CrossRefPubMed

132.

Raymond AA, Halpin SF, Alsanjari N, Cook MJ, Kitchen ND, Fish DR, Stevens JM, Harding BN, Scaravilli F, Kendall B, et al (1994) Dysembryoplastic neuroepithelial tumor. Features in 16 patients. Brain 117:461–475PubMed

133.

Reardon DA, Gajjar A, Sanford RA, Heideman RL, Walter AW, Thompson SJ, Merchant TE, Li H, Jenkins JJ, Langston J, Boyett JM, Kun LE (1998) Bithalamic involvement predicts poor outcome among children with thalamic glial tumors. Pediatr Neurosurg 29:29–35

134.

Reyes-Mugica M, Chou PM, Myint MM, Ridaura-Sanz C, Gonzales-Crussi F, Tomita T (1994) Ependymomas in children: histologic and DNA-flow cytometric study. Pediatr Pathol 14:453–466

135.

Rezai AR, Woo HH, Lee M, Cohen H, Zagzag D, Epstein FJ (1996) Disseminated ependymomas of the central nervous system. J Neurosurg 85:618–624

136.

Rickert CH (2004) Prognosis-related molecular markers in pediatric central nervous system tumors. J Neuropathol Exp Neurol 63:1211–1224

137.

Rickert CH, Paulus W (2001) Epidemiology of central nervous system neoplasms in childhood and adolescence based on the new WHO classification. Childs Nerv Syst 17:503–511CrossRefPubMed

138.

Rickert CH, Paulus W (2004) Comparative genomic hybridization in central and peripheral nervous system tumors of childhood and adolescence. J Neuropathol Exp Neurol 63:399–417PubMed

139.

Rickert CH, Sträter R, Kaatsch P, Wassmann H, Jürgens H, Dockhorn-Dworniczak B, Paulus W (2001) Pediatric high-grade astrocytomas show chromosomal imbalances distinct from adult cases. Am J Pathol 158:1525–1532PubMed

140.

Rickert CH, Wiestler OD, Paulus W (2002) Chromosomal imbalances in choroid plexus tumors. Am J Pathol 160:1105–1113PubMed

141.

Ritter AM, Hess KR, McLendon RE, Langford LA (1998) Ependymomas: MIB-1 proliferation index and survival. J Neurooncol 40:51–57CrossRefPubMed

142.

Rizk T, Mottolese C, Bouffet E, Jouvet A, Guyotat J, Bret P, Lapras C (1996) Cerebral oligodendrogliomas in children: an analysis of 15 cases. Childs Nerv Syst 12:527–529CrossRefPubMed

143.

Robertson PL, Zeltzer PM, Boyett JM, Rorke LB, Allen JC, Geyer JR, Stanley P, Li H, Albright AL, McGuire-Cullen P, Finlay JL, Stevens KR Jr, Milstein JM, Packer RJ, Wisoff J (1998) Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: a report of the Children’s Cancer Group. J Neurosurg 88:695–703

144.

Roessler K, Bertalanffy A, Jezan H, Ba-Ssalamah A, Slavc I, Czech T, Budka H (2002) Proliferative activity as measured by MIB-1 labeling index and long-term outcome of cerebellar juvenile pilocytic astrocytomas. J Neurooncol. 58:141–146

145.

Rorke LB (1987) Relationship of morphology of ependymoma in children to prognosis. Prog Exp Tumor Res 30:170–174PubMed

146.

Rosebud O, Roberts MD, Charles CB (1991) Medulloblastoma: a population-based study of 532 cases. J Neuropathol Exp Neurol 50:134–144PubMed

147.

Ross GW, Rubinstein LJ (1989) Lack of histopathological correlation of malignant ependymomas with postoperative survival. J Neurosurg 70:31–36

148.

Rumana CS, Valadka AB, Contant CF (1999) Prognostic factors in supratentorial ganglioglioma. Acta Neurochir (Wien)141:63–69

149.

Schiffer D, Giordana MT (1998) Prognosis of ependymoma. Childs Nerv Syst 14:357–361CrossRefPubMed

150.

Schiffer D, Chio A, Cravioto H, Giordana MT, Migheli A, Soffietti R, Vigliani MC (1991) Ependymoma: internal correlations among pathological signs: the anaplastic variant. Neurosurgery 29:206–210

151.

Schiffer D, Chio A, Giordana MT, Migheli A, Palma L, Pollo B, Soffietti R, Tribolo A (1991) Histologic prognostic factors in ependymoma. Childs Nerv Syst 7:177–182CrossRefPubMed

152.

Schiffer D, Chio A, Giordana MT, Pezzulo T, Vigliani MC (1993) Proliferating cell nuclear antigen expression in brain tumors, and its prognostic role in ependymomas: an immunohistochemical study. Acta Neuropathol 85:495–502CrossRefPubMed

153.

Schiffer D, Cavalla P, Migheli A, Chio A, Giordana MT, Marino S, Attanasio A (1995) Apoptosis and cell proliferation in human neuroepithelial tumors. Neurosci Lett 195:81–84CrossRefPubMed

154.

Schiffer D, Cavalla P, Migheli A, Giordana MT, Chiado-Piat L (1996) Bcl-2 distribution in neuroepithelial tumors: an immunohistochemical study. J Neurooncol 27:101–109CrossRefPubMed

155.

Schild SE, Scheithauer BW, Schomberg PJ, Hook CC, Kelly PJ, Frick L, Robinow JS, Buskirk SJ (1993) Pineal parenchymal tumors. Clinical, pathologic, and therapeutic aspects. Cancer 72:870–880PubMed

156.

Schild SE, Scheithauer BW, Haddock MG, Wong WW, Lyons MK, Marks LB, Norman MG, Burger PC (1996) Histologically confirmed pineal tumors and other germ cell tumors of the brain. Cancer 78:2564–2571CrossRefPubMed

157.

Schubert TEO, Cervos-Navarro J (1998) The histopathological and clinical relevance of apoptotic cell death in medulloblastomas. J Neuropathol Exp Neurol 57:10–15PubMed

158.

Sgouros S, Fineron PW, Hockley AD (1995) Cerebellar astrocytoma of childhood: long-term follow-up. Childs Nerv Syst 11:89–96CrossRefPubMed

159.

Smoots DW, Geyer JR, Lieberman DM, Berger MS (1998) Predicting disease progression in childhood cerebellar astrocytoma. Childs Nerv Syst 14:636–648CrossRefPubMed

160.

Sobel EL, Gilles FH, Tavare CJ, Leviton A, Hedley-Whyte ET (1997) Prognosis for children with supratentorial neuroglial tumors. Pediatr Pathol Lab Med 17:755–767

161.

Sugita Y, Shigemori M, Okamoto K, Morimatsu M, Arakawa M, Nakayama K (2000) Clinicopathological study of pleomorphic xanthoastrocytoma: correlation between histological features and prognosis. Pathol Int 50:703–708CrossRefPubMed

162.

Sure U, Berghorn WJ, Bertalanffy H, Wakabayashi T, Yoshida Y, Sugita K, Seeger W (1995) Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single insitute. Acta Neurochir (Wien) 132:59–65

163.

Sutton LN, Goldwein J, Perilongo G, Lang B, Schut L, Rorke L, Packer R (1990–1991) Prognostic factors in childhood ependymomas. Pediatr Neurosurg 16:57–65PubMed

164.

Tan TC, Ho LC, Yu CP, Cheung FC (2004) Pleomorphic xanthoastrocytoma: report of two cases and review of the prognostic factors. J Clin Neurosci 11:203–207CrossRefPubMed

165.

Thiessen B, Finlay J, Kulkarni R, Rosenblum MK (1998) Astroblastoma: does histology predict biological behavior? J Neurooncol 40:59–65CrossRefPubMed

166.

Tihan T, Fisher PG, Kepner JL, Godfraind C, McComb RD, Goldthwaite PT, Burger PC (1999) Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome. J Neuropathol Exp Neurol 58:1061–1068PubMed

167.

Tomita T, Yasue M, Engelhard HH, McLone DG, Gonzalez-Crussi F, Bauer KD (1988) Flow cytometric DNA analysis of medulloblastoma. Prognostic implication of aneuploidy. Cancer 61:744–749PubMed

168.

Tomlinson FH, Scheithauer BW, Hayostek CJ, Parisi JE, Meyer FB, Shaw EG, Weiland TL, Katzmann JA, Jack CR (1994) The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow-cytometric study. J Child Neurol 9:301–310PubMed

169.

Tsumanuma I, Tanaka R, Washiyama K (1999) Clinicopathological study of pineal parenchymal tumors: correlation between histopathological features, proliferative potential, and prognosis. Brain Tumor Pathol 16:61–68PubMed

170.

Uematsu Y, Tsuura Y, Miyamoto K, Itakura T, Hayashi S, Komai N (1992) The recurrence of primary intracranial germinomas. Special reference to germinoma with STGC (syncytiotrophoblastic giant cell). J Neurooncol 13:247–256CrossRefPubMed

171.

Vajtai I, Varga Z (1998) Prognostic markers of pleomorphic xanthoastrocytoma. Histopathology 33:391CrossRef

172.

Varga Z, Vajtai I (1998) Prognostic markers in the histopathological diagnosis of tumors of the choroid plexus. Orv Hetil 139:761–765PubMed

173.

Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski M, Flamm ES, Epstein FJ, Miller DC (1994) Craniopharyngiomas: a clinico-pathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery 35:1001–1010

174.

Wiestler OD, Lopes BS, Green AJ, Vinters HV (2000) Tuberous sclerosis complex and subependymal giant cell astrocytoma. In: Kleihues P, Cavenee WK (eds) Pathology and genetics. Tumours of the central nervous system. IARC, Lyon, pp 227–230

175.

Wolf HK, Muller MB, Spanle M, Zentner J, Schramm J, Wiestler OD (1994) Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. Acta Neuropathol 88:166–173PubMed

176.

Wolff JE, Sajedi M, Brant R, Coppes MJ, Egeler RM (2002) Choroid plexus tumours. Br J Cancer 87:1086–1091CrossRefPubMed

177.

Wolfsberger S, Fischer I, Hoftberger R, Birner P, Slavc I, Dieckmann K, Czech T, Budka H, Hainfellner J (2004) Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma. Am J Surg Pathol 28:914–920PubMed

178.

Woodburn RT, Azzarelli B, Montebello JF, Goss IE (2001) Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors. J Neurooncol 52:57–62CrossRefPubMed

179.

Yang HJ, Nam DH, Wang KC, Kim YM, Chi JG, Cho BK (1999) Supratentorial primitive neuroectodermal tumor in children: clinical features, treatment outcome and prognostic factors. Childs Nerv Syst 15:377–383CrossRefPubMed

180.

Zamecnik J, Snuderl M, Eckschlager T, Chanova M, Hladikova M, Tichy M, Kodet R (2003) Pediatric intracranial ependymomas: prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Pathol 16:980–991CrossRefPubMed

Title: Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence
Authors: Christian H. Rickert
Werner Paulus
Publication date: 01-01-2005
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2005
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-004-0959-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2005

Pathogenesis of prion diseases

Kurt Jellinger Prize for Outstanding Scientific Writing in Neuropathology

The role of electron microscopy in neuropathology

Editorial

Demyelination in canine distemper virus infection: a review

Change of Editor-in-Chief—but no farewell to scientific arms