Skip to main content
Top
Published in: Journal of Neuro-Oncology 1/2015

Open Access 01-05-2015 | Laboratory Investigation

Contrast enhancement pattern predicts poor survival for patients with non-WNT/SHH medulloblastoma tumours

Authors: Maria Łastowska, Elżbieta Jurkiewicz, Joanna Trubicka, Paweł Daszkiewicz, Monika Drogosiewicz, Katarzyna Malczyk, Wiesława Grajkowska, Ewa Matyja, Bożena Cukrowska, Maciej Pronicki, Marta Perek-Polnik, Danuta Perek, Bożenna Dembowska-Bagińska

Published in: Journal of Neuro-Oncology | Issue 1/2015

Login to get access

Abstract

Recent studies revealed the biological heterogeneity of medulloblastoma, with the existence of at least four groups which are associated with several clinical and morphological features. We investigated for further correlations between molecular types, location of tumours, their contrast enhancement pattern and survival of patients. Altogether 76 tumours were analyzed and molecular subtypes were identified by immunohistochemistry using representative antibodies, detection of chromosome 6 monosomy and CTNNB1 mutation. The site of the tumour was assessed on diagnosis using Magnetic Resonance images and intra-operative surgical reports. In addition, the gadolinium enhancement pattern was also investigated in pre-treatment tumours. Cerebellar hemispheric location was associated with SHH tumours (p < 0.001), as opposed to midline location being typical for WNT and non-WNT/SHH tumours. Remarkably, for patients with non-WNT/SHH tumours, the extensive gadolinium enhancement pattern (present in >75 % of tumour volume) predicted worse OS and EFS than for those with none/weak or heterogeneous enhancement (>10–75 % of tumour volume), (both p < 0.001). Our analysis indicates that distribution of the medulloblastoma tumours location is related to the biological characteristics of tumour. Importantly, the enhancement pattern of the tumour may be a clinically useful prognostic marker for patients with non-WNT/SHH medulloblastomas.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3(8):e3088. doi:10.1371/journal.pone.0003088 CrossRefPubMedCentralPubMed Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3(8):e3088. doi:10.​1371/​journal.​pone.​0003088 CrossRefPubMedCentralPubMed
2.
go back to reference Northcott PA, Korshunov A, Witt H et al (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29:1408–1414CrossRefPubMed Northcott PA, Korshunov A, Witt H et al (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29:1408–1414CrossRefPubMed
3.
go back to reference Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, GreulichH Berhoukim R, Amani V, Goumnerova L, Eberhart CG, LauCC Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL (2011) Integrativegenomic analysis of medulloblastoma identifies amolecular subgroup that drives poor clinical outcome. J Clin Oncol 29:1424–1430CrossRefPubMedCentralPubMed Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, GreulichH Berhoukim R, Amani V, Goumnerova L, Eberhart CG, LauCC Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL (2011) Integrativegenomic analysis of medulloblastoma identifies amolecular subgroup that drives poor clinical outcome. J Clin Oncol 29:1424–1430CrossRefPubMedCentralPubMed
5.
go back to reference Kool M, Korshunov A, Remke M, Jones DTW, Schlanstein M, Northcott PA et al (2012) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol 123:473–484CrossRefPubMedCentralPubMed Kool M, Korshunov A, Remke M, Jones DTW, Schlanstein M, Northcott PA et al (2012) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol 123:473–484CrossRefPubMedCentralPubMed
6.
go back to reference Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH, Ligon KL (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–134CrossRefPubMedCentralPubMed Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH, Ligon KL (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–134CrossRefPubMedCentralPubMed
7.
go back to reference Grammel D, Warmuth-Metz M, von Bueren AO, Kool M, Pietsch T, Kretzschmar HA, Rowitch DH, Rutkowski S, Pfister SM, Schüller U (2012) Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol 123:601–614CrossRefPubMed Grammel D, Warmuth-Metz M, von Bueren AO, Kool M, Pietsch T, Kretzschmar HA, Rowitch DH, Rutkowski S, Pfister SM, Schüller U (2012) Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol 123:601–614CrossRefPubMed
9.
go back to reference Teo WY, Shen J, Su JM, Yu A, Wang J, Chow WY, Li X, Jones J, Dauser R, Whitehead W, Adesina AM, Chintagumpala M, Man TK, Lau CC (2013) Implications of tumor location on subtypes of medulloblastoma. Pediatr Blood Cancer 60:1408–1410. doi:10.1002/pbc.24511 CrossRefPubMed Teo WY, Shen J, Su JM, Yu A, Wang J, Chow WY, Li X, Jones J, Dauser R, Whitehead W, Adesina AM, Chintagumpala M, Man TK, Lau CC (2013) Implications of tumor location on subtypes of medulloblastoma. Pediatr Blood Cancer 60:1408–1410. doi:10.​1002/​pbc.​24511 CrossRefPubMed
10.
go back to reference Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT, Shih D, Remke M, Schubert S, Bouffet E, Fisher PG, Partap S, Vogel H, Taylor MD, Cho YJ, Yeom KW (2014) MRI Surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol 35:1263–1269. doi:10.3174/ajnr.A3990 CrossRefPubMed Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT, Shih D, Remke M, Schubert S, Bouffet E, Fisher PG, Partap S, Vogel H, Taylor MD, Cho YJ, Yeom KW (2014) MRI Surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol 35:1263–1269. doi:10.​3174/​ajnr.​A3990 CrossRefPubMed
11.
go back to reference Gottardo NG, Hansford JR, McGlade JP et al (2014) Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group. Acta Neuropathol 127:189–201CrossRefPubMedCentralPubMed Gottardo NG, Hansford JR, McGlade JP et al (2014) Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group. Acta Neuropathol 127:189–201CrossRefPubMedCentralPubMed
12.
go back to reference Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–10914CrossRefPubMedCentralPubMed Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–10914CrossRefPubMedCentralPubMed
13.
go back to reference Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, Kenney AM, Brat DJ, Perry A, Yong WH, Taylor RE, Bailey S, Clifford SC, Gilbertson RJ (2011) Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol 121:381–396CrossRefPubMedCentralPubMed Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, Kenney AM, Brat DJ, Perry A, Yong WH, Taylor RE, Bailey S, Clifford SC, Gilbertson RJ (2011) Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol 121:381–396CrossRefPubMedCentralPubMed
14.
go back to reference Chang CH, Housepian EM, Herbert C Jr (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93:1351–1359CrossRefPubMed Chang CH, Housepian EM, Herbert C Jr (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93:1351–1359CrossRefPubMed
15.
go back to reference Picard D, Miller S, Hawkins CE, Bouffet E, Rogers HA, Chan TS, Kim SK, Ra YS, Fangusaro J, Korshunov A, Toledano H, Nakamura H, Hayden JT, Chan J, Lafay-Cousin L, Hu P, Fan X, Muraszko KM, Pomeroy SL, Lau CC, Ng HK, Jones C, Van Meter T, Clifford SC, Eberhart C, Gajjar A, Pfister SM, Grundy RG, Huang A (2012) Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis. Lancet Oncol 13:838–848CrossRefPubMedCentralPubMed Picard D, Miller S, Hawkins CE, Bouffet E, Rogers HA, Chan TS, Kim SK, Ra YS, Fangusaro J, Korshunov A, Toledano H, Nakamura H, Hayden JT, Chan J, Lafay-Cousin L, Hu P, Fan X, Muraszko KM, Pomeroy SL, Lau CC, Ng HK, Jones C, Van Meter T, Clifford SC, Eberhart C, Gajjar A, Pfister SM, Grundy RG, Huang A (2012) Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis. Lancet Oncol 13:838–848CrossRefPubMedCentralPubMed
16.
go back to reference Bühring U, Strayle-Batra M, Freudenstein D, Scheel-Walter HG, Küker W (2002) MRI features of primary, secondary and metastatic medulloblastoma. Eur Radiol 12:1342–1348CrossRefPubMed Bühring U, Strayle-Batra M, Freudenstein D, Scheel-Walter HG, Küker W (2002) MRI features of primary, secondary and metastatic medulloblastoma. Eur Radiol 12:1342–1348CrossRefPubMed
17.
go back to reference Jaiswal AK, Mahapatra AK, Sharma MC (2004) Cerebellopointine angle medulloblastoma. J Clin Neurosci 11:42–45CrossRefPubMed Jaiswal AK, Mahapatra AK, Sharma MC (2004) Cerebellopointine angle medulloblastoma. J Clin Neurosci 11:42–45CrossRefPubMed
18.
go back to reference Yeom KW, Mobley BC, Lober RM, Andre JB, Partap S, Vogel H, Barnes PD (2013) Distinctive MRI features of pediatric medulloblastoma subtypes. AJR Am J Roentgenol 200:895–903CrossRefPubMed Yeom KW, Mobley BC, Lober RM, Andre JB, Partap S, Vogel H, Barnes PD (2013) Distinctive MRI features of pediatric medulloblastoma subtypes. AJR Am J Roentgenol 200:895–903CrossRefPubMed
19.
go back to reference Hervey-Jumper SL, Garton HJ, Lau D, Altshuler D, Quint DJ, Robertson PL, Muraszko KM, Maher CO (2014) Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma. J Neurosurg Pediatr 14:121–128CrossRefPubMed Hervey-Jumper SL, Garton HJ, Lau D, Altshuler D, Quint DJ, Robertson PL, Muraszko KM, Maher CO (2014) Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma. J Neurosurg Pediatr 14:121–128CrossRefPubMed
Metadata
Title
Contrast enhancement pattern predicts poor survival for patients with non-WNT/SHH medulloblastoma tumours
Authors
Maria Łastowska
Elżbieta Jurkiewicz
Joanna Trubicka
Paweł Daszkiewicz
Monika Drogosiewicz
Katarzyna Malczyk
Wiesława Grajkowska
Ewa Matyja
Bożena Cukrowska
Maciej Pronicki
Marta Perek-Polnik
Danuta Perek
Bożenna Dembowska-Bagińska
Publication date
01-05-2015
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2015
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1779-0

Other articles of this Issue 1/2015

Journal of Neuro-Oncology 1/2015 Go to the issue