Summary
Assessment of brain tumor proliferative potential provides important prognostic information that supplements standard histopathologic grading. Many laboratories rely on mitotic figures to quantify the proliferative potential of brain tumors, but this conventional cellular proliferative index is subject to inter-observer variability and not consistently predictive for low-and high-grade tumors. Recent advancements in technology have made it possible to use proliferative indices as a standard supplement in pathology laboratories. Non-invasive tumor tissue measurements of cell proliferation can be performed using– bromodeoxyuridine labeling index (BrdU LI), flow cytometry (FCM), MIB-1 antibody to the Ki-67 antigen (MIB-1), proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing regions (AgNOR). Each of these assays has been described in the literature with respect to its ability to predict tumor grade or outcome. At the present time MIB-1 and AgNOR are the simplest and most reliable of these techniques. In addition, advances in our understanding of the genetic alterations associated with proliferation promise to provide more specific markers of proliferative potential. Beyond the pathology laboratory, radiographic studies such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and most recently magnetic resonance spectroscopy (MRS) have been used as follow-up measures, assessing response to treatment and tumor recurrence, rather than as predictors of response to treatment. These radiographic tools, however, have the potential to provide an assessment of tumor proliferation without the need for invasive measures. In this article, we present a review of the current techniques utilized to understand the proliferative potential of brain tumors.
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References
CM Abramovich RA. Prayson (1998) ArticleTitleMIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors Hum Pathol 29 1420–1427 Occurrence Handle10.1016/S0046-8177(98)90010-7 Occurrence Handle9865827
A. Ahyai (1998) ArticleTitleFlow cytometric analysis of cellular DNA content in human astrocytomas and oligodendrogliomas Neurosurg Rev 11 177–187 Occurrence Handle10.1007/BF01794685
D Ancri JY. Basset (1980) ArticleTitleDiagnosis of cerebral metastases by thallium 201 Br J Radiol 53 443–453 Occurrence Handle7388277
FG Barker MD Prados SM Chang et al. (1996) ArticleTitleBromodeoxyuridine labeling index in glioblastoma multiforme: relation to radiation response, age, and survival Int J Radiat Oncol Biol Phys 34 803–808 Occurrence Handle10.1016/0360-3016(95)02027-6 Occurrence Handle8598356
KL Black T Emerick C Hoh et al. (1994) ArticleTitleThallium-201 SPECT and positron emission tomography equal predictors of glioma grade and recurrence Neurol Res 16 93–96 Occurrence Handle7914007
AP Boon H. Sharif (1999) ArticleTitleValue of AgNOR method in predicting recurrence of meningioma J Clin Pathol 42 1002–1003
R Bravo R Frank PA Blundell et al. (1987) ArticleTitleCyclin/PCNA is the auxiliary protein of DNA polymerase-delta Nature 326 515–517 Occurrence Handle10.1038/326515a0 Occurrence Handle2882423
PC Burger T Shibata P. Kleihues (1986) ArticleTitleThe use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology Am J Surg Pathol 10 611–617 Occurrence Handle2428262
JE Celis A. Celis (1985) ArticleTitleCell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase Proc Natl Acad Sci USA 82 3262–3266 Occurrence Handle2860667
KG Cho T Hoshino T Nagashima et al. (1986) ArticleTitlePrediction of tumor doubling time in recurrent meningiomas. Cell kinetics studies with bromodeoxyuridine labeling J Neurosurg 65 790–794 Occurrence Handle3772477
R Chung J Whaley N Kley et al. (1991) ArticleTitleTP53 gene mutations and 17p deletions in human astrocytoma Genes Chromosomes Cancer 3 323–331 Occurrence Handle1686725
Coons SW. (1996). Proliferation Markers in the Evaluation fo Gliomas, in Special Course AANP. Vancouver, Canada
SW Coons JR Davis DL. Way (1988) ArticleTitleCorrelation of DNA content and histology in prognosis of astrocytomas Am J Clin Pathol 90 289–293 Occurrence Handle2843034
Coons SW, Johnson PC, Pearl DK. (1994). Prognostic significance of flow cytometry deoxyribonucleic acid analysis of human astrocytomas. Neurosurgery 35: 119–125; discussion 125–116
Coons SW, Johnson PC, Pearl DK. (1997). The prognostic significance of Ki-67 labeling indices for oligodendrogliomas. Neurosurgery 41: 878–884; discussion 884–875
Coons SW, Johnson PC, Pearl DK et al. (1994). Prognostic significance of flow cytometry deoxyribonucleic acid analysis of human oligodendrogliomas. Neurosurgery 34: 680–687; discussion 687
J Crocker JC Macartney PJ. Smith (1988) ArticleTitleCorrelation between DNA flow cytometric and nucleolar organizer region data in non-Hodgkin’s lymphomas J Pathol 154 151–156 Occurrence Handle10.1002/path.1711540207 Occurrence Handle3280766
JM Cunningham DW Kimmel BW Scheithauer et al. (1997) ArticleTitleAnalysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value J Neurosurg 86 121–130 Occurrence Handle8988090
M Danova W Giaretti F Merlo et al. (1991) ArticleTitlePrognostic significance of nuclear DNA content in human neuroepithelial tumors Int J Cancer 48 663–667 Occurrence Handle2071227
AO De Beeck P. Caillet-Fauquet (1997) ArticleTitleViruses and the cell cycle Prog Cell Cycle Res 3 1–19 Occurrence Handle9552402
De Witte O, Levivier M, Violon P et al. (1996). Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose in the low-grade glioma. Neurosurgery 39: 470–476; discussion 476–477
F Dehghani W Schachenmayr A Laun et al. (1998) ArticleTitlePrognostic implication of histopathological, immunohistochemical and clinical features of oligodendrogliomas: a study of 89 cases Acta Neuropathol (Berl) 95 493–504 Occurrence Handle10.1007/s004010050830
D Delbeke C Meyerowitz RL Lapidus et al. (1995) ArticleTitleOptimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET Radiology 195 47–52 Occurrence Handle7892494
G. Di Chiro (1987) ArticleTitlePositron emission tomography using [18F] fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool Invest Radiol 22 360–371 Occurrence Handle3496318
G Di Chiro RL DeLaPaz RA Brooks et al. (1982) ArticleTitleGlucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography Neurology 32 1323–1329 Occurrence Handle6983044
G Di Chiro J Hatazawa DA Katz et al. (1987) ArticleTitleGlucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study Radiology 164 521–526 Occurrence Handle3496626
CM Dirven J Koudstaal JJ Mooij et al. (1998) ArticleTitleThe proliferative potential of the pilocytic astrocytoma: the relation between MIB-1 labeling and clinical and neuro-radiological follow-up J Neurooncol 37 9–16 Occurrence Handle10.1023/A:1005905009449 Occurrence Handle9525833
C Dowling AW Bollen SM Noworolski et al. (2001) ArticleTitlePreoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens AJNR Am J Neuroradiol 22 604–612 Occurrence Handle11290466
MH Dreyling SK Bohlander MO Adeyanju et al. (1995) ArticleTitleDetection of CDKN2 deletions in tumor cell lines and primary glioma by interphase fluorescence in situ hybridization Cancer Res 55 984–988 Occurrence Handle7867008
A Falini G Calabrese D Origgi et al. (1996) ArticleTitleProton magnetic resonance spectroscopy and intracranial tumours: clinical perspectives J Neurol 243 706–714 Occurrence Handle10.1007/BF00873976 Occurrence Handle8923303
J Frahm H Bruhn W Hanicke et al. (1991) ArticleTitleLocalized proton NMR spectroscopy of brain tumors using short-echo time STEAM sequences J Comput Assist Tomogr 15 915–922 Occurrence Handle1939768
DA Freeman L Wu AJ. Levine (1999) ArticleTitleFunctions of the MDM2 oncoprotein Cell Mol Life Sci 55 96–107 Occurrence Handle10.1007/s000180050273 Occurrence Handle10065155
A Freese D O’Rourke K Judy et al. (1994) ArticleTitleThe application of 5-bromodeoxyuridine in the management of CNS tumors J Neurooncol 20 81–95 Occurrence Handle10.1007/BF01057964 Occurrence Handle7807187
ML Friedlander DW Hedley IW. Taylor (1984) ArticleTitleClinical and biological significance of aneuploidy in human tumours J Clin Pathol 37 961–974 Occurrence Handle6381555
T Fujimaki M Matsutani O Nakamura et al. (1991) ArticleTitleCorrelation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults Cancer 67 1629–1634 Occurrence Handle2001552
V Ganju RB Jenkins JR O’Fallon et al. (1994) ArticleTitlePrognostic factors in gliomas. A multivariate analysis of clinical, pathologic, flow cytometric, cytogenetic, and molecular markers Cancer 74 920–927 Occurrence Handle8039120
R Garcia A Bueno S Castanon et al. (1997) ArticleTitleStudy of the DNA content by flow cytometry and proliferation in 281 brain tumors Oncology 54 112–117 Occurrence Handle9075781
J Gerdes H Lemke H Baisch et al. (1984) ArticleTitleCell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67 J Immunol 133 1710–1715 Occurrence Handle6206131
HK Haapasalo PK Sallinen PT Helen et al. (1993) ArticleTitleComparison of three quantitation methods for PCNA immunostaining: applicability and relation to survival in 83 astrocytic neoplasms J Pathol 171 207–214 Occurrence Handle10.1002/path.1711710309 Occurrence Handle7903983
PA Hall J Crocker A Watts et al. (1988) ArticleTitleA comparison of nucleolar organizer region staining and Ki-67 immunostaining in non-Hodgkin’s lymphoma Histopathology 12 373–381 Occurrence Handle2453436
A Hara N Sakai H Yamada et al. (1991) ArticleTitleRapid detection of proliferating potential in human brain tumors by nucleolar organizer region staining on squash preparations J Cancer Res Clin Oncol 117 510–514 Occurrence Handle10.1007/BF01613280 Occurrence Handle1720782
J He JJ Olson CD. James (1995) ArticleTitleLack of p16(INK4) or retinoblastoma protein (pRb), or amplification-associated overexpression of CDK4 is observed in distinct subsets of malignant glial cells Cancer Res 55 4833–4836 Occurrence Handle7585516
JW Henson BL Schnitker KM Correa et al. (1995) ArticleTitleThe retinoblastoma gene is involved in malignant progression of astrocytomas Ann Neurol 36 714–721 Occurrence Handle10.1002/ana.410360505
T Higa S Maetani K Yoichiro et al. (2001) ArticleTitleTI-201 SPECT compared with histopathologic grade in the prognostic assessment of cerebral gliomas Clin Nucl Med 26 119–124 Occurrence Handle10.1097/00003072-200102000-00006 Occurrence Handle11201468
T. Hoshino (1984) ArticleTitleA commentary on the biology and growth kinetics of low-grade and high- grade gliomas J Neurosurg 61 895–900 Occurrence Handle6491735
T Hoshino D Ahn MD Prados et al. (1993) ArticleTitlePrognostic significance of the proliferative potential of intracranial gliomas measured by bromodeoxyuridine labeling Int J Cancer 53 550–555 Occurrence Handle8382191
T Hoshino T Nagashima KG Cho et al. (1986) ArticleTitleS phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine Int J Cancer 38 369–374 Occurrence Handle3527993
T Hoshino T Nagashima JA Murovic et al. (1986) ArticleTitleProliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine Cancer 58 1466–1472 Occurrence Handle2427189
T Hoshino M Prados CB Wilson et al. (1989) ArticleTitlePrognostic implications of the bromodeoxyuridine labeling index of human gliomas J Neurosurg 71 335–341 Occurrence Handle2549222
T Hoshino LA Rodriguez KG Cho et al. (1988) ArticleTitlePrognostic implications of the proliferative potential of low-grade astrocytomas J Neurosurg 69 839–842 Occurrence Handle3193189
WM Howell DA. Black (1980) ArticleTitleControlled silver-staining of nucleolus organizer regions with a protective colloidal developer: a 1-step method Experientia 36 1014–1015 Occurrence Handle10.1007/BF01953855 Occurrence Handle6160049
K Ichimura EE Schmidt HM Goike et al. (1996) ArticleTitleHuman glioblastomas with no alterations of the CDKN2 (p16, INK4A, MTS1) and CDK4 genes have frequent mutations of the retinoblastoma gene Oncogene 13 1065–1072 Occurrence Handle8806696
M Ide M Jimbo M Yamamoto et al. (1995) ArticleTitleGrowth rate of intracranial meningioma: tumor doubling time and proliferating cell nuclear antigen staining index Neurol Med Chir (Tokyo) 35 289–293
S Ito KL Chandler MD Prados et al. (1994) ArticleTitleProliferative potential and prognostic evaluation of low-grade astrocytomas J Neurooncol 19 1–9 Occurrence Handle10.1007/BF01051043 Occurrence Handle7815099
T Iuchi Y Iwadate H Namba et al. (1999) ArticleTitleGlucose and methionine uptake and proliferative activity in meningiomas Neurol Res 21 640–644 Occurrence Handle10555183
E Jaros RH Perry L Adam et al. (1992) ArticleTitlePrognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours Br J Cancer 66 373–385 Occurrence Handle1503912
J Jen W Harper SH Bigner et al. (1994) ArticleTitleDeletion of p16 and p15 genes in brain tumors Cancer Res 54 6353–6358 Occurrence Handle7987828
K Kajiwara T Nishizaki T Orita et al. (1990) ArticleTitleSilver colloid staining technique for analysis of glioma malignancy J Neurosurg 73 113–117 Occurrence Handle1693670
B Kaschten A Stevenaert B Sadzot et al. (1998) ArticleTitlePreoperative evaluation of 54 gliomas by PET with fluorine-18- fluorodeoxyglucose and/or carbon-11-methionine J Nucl Med 39 778–785 Occurrence Handle9591574
S Khoshyomn H Maier T Morimura et al. (1993) ArticleTitleImmunostaining for proliferating cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens Acta Neuropathol 86 582–589 Occurrence Handle10.1007/BF00294296
Kim DK, Hoyt J, Bacchi C et al. (1993). Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins. Neurosurgery 33: 619–625; discussion 625–616
S Kosuda H Fujii S Aoki et al. (1994) ArticleTitlePrediction of survival in patients with suspected recurrent cerebral tumors by quantitative thallium-201 single photon emission computed tomography Int J Radiat Oncol Biol Phys 30 1201–1206 Occurrence Handle7961030
Kreipe H ZR, Fischer L et al. Immunocytochemical assessment of cell proliferation, In: Hofstadter FKR, Rushoff J (eds) Cell Proliferation Assessment in Oncology: VIrchow Arch, 1995, Vol 427, pp 324–326
JV Lafuente K Alkiza JM Garibi et al. (2000) ArticleTitleBiologic parameters that correlate with the prognosis of human gliomas Neuropathology 20 176–183 Occurrence Handle10.1046/j.1440-1789.2000.00329.x Occurrence Handle11132932
KR Lamborn MD Prados SB Kaplan et al. (1999) ArticleTitleFinal report on the University of California-San Francisco experience with bromodeoxyuridine labeling index as a prognostic factor for the survival of glioma patients Cancer 85 925–935 Occurrence Handle10.1002/(SICI)1097-0142(19990215)85:4<925::AID-CNCR22>3.0.CO;2-Q Occurrence Handle10091772
G Landberg G. Roos (1991) ArticleTitleAntibodies to proliferating cell nuclear antigen as S phase probes in flow cytometric cell cycle analysis Cancer Res 51 4570–4574 Occurrence Handle1678682
KS Lee T Hoshino LA Rodriguez et al. (1990) ArticleTitleBromodeoxyuridine labeling study of intracranial meningiomas: proliferative potential and recurrence Acta Neuropathol 80 311–317 Occurrence Handle10.1007/BF00294650 Occurrence Handle2399811
MD Linden FX Torres J Kubus et al. (1992) ArticleTitleClinical application of morphologic and immunocytochemical assessments of cell proliferation Am J Clin Pathol 97 S4–S13 Occurrence Handle1575220
NS Litofsky TC Mix SP Baker et al. (1998) ArticleTitleKi-67 (clone MIB-1) proliferation index in recurrent glial neoplasms: no prognostic significance Surg Neurol 50 579–585 Occurrence Handle10.1016/S0090-3019(97)00312-1 Occurrence Handle9870820
DN Louis S Edgerton AD Thor et al. (1991) ArticleTitleProliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: a comparative study Acta Neuropathol 81 675–679 Occurrence Handle10.1007/BF00296379 Occurrence Handle1679278
A Maillo P Diaz A Blanco et al. (1999) ArticleTitleProportion of S phase tumor cells measured by flow cytometry is an independent prognostic factor in meningioma tumors Cytometry 38 118–123 Occurrence Handle10.1002/(SICI)1097-0320(19990615)38:3<118::AID-CYTO5>3.0.CO;2-J Occurrence Handle10397331
PE McKeever DA Ross MS Strawderman et al. (1997) ArticleTitleA comparison of the predictive power for survival in gliomas provided by MIB-1, bromodeoxyuridine and proliferating cell nuclear antigen with histopathologic and clinical parameters J Neuropathol Exp Neurol 56 798–805 Occurrence Handle9210876
PE McKeever MS Strawderman B Yamini et al. (1998) ArticleTitleMIB-1 proliferation index predicts survival among patients with grade II astrocytoma J Neuropathol Exp Neurol 57 931–936 Occurrence Handle9786243
WE. Mercer (1998) ArticleTitleChecking on the cell cycle J Cell Biochem 30 50–54 Occurrence Handle10.1002/(SICI)1097-4644(1998)72:30/31+<50::AID-JCB8>3.0.CO;2-8
A Merlo JG Herman L Mao et al. (1995) ArticleTitle5′CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/CDKN2/MTS1 Nature Med 1 686–692 Occurrence Handle10.1038/nm0795-686 Occurrence Handle7585152
Montine TJ, Vandersteenhoven JJ, Aguzzi A et al. (1994). Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasms. Neurosurgery 34: 674–678; discussion 678–679
SJ Mork TB Halvorsen KF Lindegaard et al. (1986) ArticleTitleOligodendroglioma. Histologic evaluation and prognosis J Neuropathol Exp Neurol 45 65–78 Occurrence Handle3941327
T Nagashima SJ DeArmond J Murovic et al. (1985) ArticleTitleImmunocytochemical demonstration of S phase cells by anti- bromodeoxyuridine monoclonal antibody in human brain tumor tissues Acta Neuropathol 67 155–159 Occurrence Handle10.1007/BF00688136 Occurrence Handle2992212
M Nakamura N Konishi S Tsunoda et al. (1997) ArticleTitleRetinoblastoma protein expression and MIB-1 correlate with survival of patients with malignant astrocytoma Cancer 80 242–249 Occurrence Handle10.1002/(SICI)1097-0142(19970715)80:2<242::AID-CNCR12>3.0.CO;2-U Occurrence Handle9217037
S Nakasu M Nakajima K Matsumura et al. (1995) ArticleTitleMeningioma: proliferating potential and clinicoradiological features Neurosurgery 37 1049–1055 Occurrence Handle8584144
T Nishi J Kuratsu H Takeshima et al. (1999) ArticleTitlePrognostic significance of the MIB-1 labeling index for patient with craniopharyngioma Int J Mol Med 3 157–161 Occurrence Handle9917523
T Nishizaki N Ohshita Y Nagatsugu et al. (1993) ArticleTitleClinical evaluation of DNA index in human brain tumors J Neurooncol 17 9–13 Occurrence Handle10.1007/BF01054268 Occurrence Handle8120576
Y Ono T Tamiya T Ichikawa et al. (1996) ArticleTitleMalignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indeces J Neuropathol Exp Neurol 55 1026–1031 Occurrence Handle8857999
N Oriuchi M Tamura T Shibazaki et al. (1993) ArticleTitleClinical evaluation of thallium-201 SPECT in supratentorial gliomas: relationship to histologic grade, prognosis and proliferative activities J Nucl Med 34 2085–2089 Occurrence Handle8254391
D Ott J Hennig T. Ernst (1993) ArticleTitleHuman brain tumors: assessment with in vivo proton MR spectroscopy Radiology 186 745–752 Occurrence Handle8430183
KH Plate J Ruschoff J Behnke et al. (1990) ArticleTitleProliferative potential of human brain tumours as assessed by nucleolar organizer regions (AgNORs) and Ki67-immunoreactivity Acta Neurochir 104 103–109 Occurrence Handle10.1007/BF01842827
Raghavan R, Dickey WT, Jr., Margraf LR et al. (2000). Proliferative activity in craniopharyngiomas: clinicopathological correlations in adults and children. Surg Neurol 54: 241–247; discussion 248
G Reifenberger L Liu K Ichimura et al. (1993) ArticleTitleAmplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations Cancer Res 53 2736–2739 Occurrence Handle8504413
A Riccardi M Danova G Wilson et al. (1988) ArticleTitleCell kinetics in human malignancies studied with in vivo administration of bromodeoxyuridine and flow cytometry Cancer Res 48 6238–6245 Occurrence Handle3167869
Ritter AM, Sawaya R, Hess KR et al. (1994). Prognostic significance of bromodeoxyuridine labeling in primary and recurrent glioblastoma multiforme. Neurosurgery 35: 192–198; discussion 198
M Rodrigues AT Fonseca D Salgado et al. (1993) ArticleTitle99Tcm-HMPAO brain SPECT in the evaluation of prognosis after surgical resection of astrocytoma. Comparison with other noninvasive imaging techniques (CT, MRI and 201Tl SPECT) Nucl Med Commun 14 1050–1060 Occurrence Handle8295760
EJ Rushing DF Brown CL Hladik et al. (1998) ArticleTitleCorrelation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype Mod Pathol 11 464–470 Occurrence Handle9619600
PK Sallinen HK Haapasalo T Visakorpi et al. (1994) ArticleTitlePrognostication of astrocytoma patient survival by Ki-67 (MIB-1), PCNA, and S phase fraction using archival paraffin-embedded samples J Pathol 174 275–282 Occurrence Handle10.1002/path.1711740407 Occurrence Handle7884589
I Salmon R. Kiss (1993) ArticleTitleRelationship between proliferative activity and ploidy level in a series of 530 human brain tumors, including astrocytomas, meningiomas, schwannomas, and metastases Hum Pathol 24 329–335 Occurrence Handle10.1016/0046-8177(93)90045-I Occurrence Handle8454277
D Schiffer A Chio MT Giordana et al. (1993) ArticleTitleProliferating cell nuclear antigen expression in brain tumors, and its prognostic role in ependymomas: an immunohistochemical study Acta Neuropathol 85 495–502 Occurrence Handle10.1007/BF00230488 Occurrence Handle8098564
EE Schmidt K Ichimura G Reifenberger et al. (1994) ArticleTitleCDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas Cancer Res 54 6321–6324 Occurrence Handle7987821
RB Schwartz BL Holman JF Polak et al. (1998) ArticleTitleDual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy J Neurosurg 89 60–68 Occurrence Handle9647173
Shibuya M, Hoshino T, Ito S et al. (1992). Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling. Neurosurgery 30: 494–497; discussion 497–498
T Shiraishi K Tabuchi T Mineta et al. (1991) ArticleTitleNucleolar organizer regions in various human brain tumors J Neurosurg 74 979–984 Occurrence Handle2033460
KK Shivji MK Kenny RD. Wood (1992) ArticleTitleProliferating cell nuclear antigen is required for DNA excision repair Cell 69 367–374 Occurrence Handle10.1016/0092-8674(92)90416-A Occurrence Handle1348971
JS Smith B Alderete Y Minn et al. (1999) ArticleTitleLocalization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype Oncogene 18 4144–4152 Occurrence Handle10.1038/sj.onc.1202759 Occurrence Handle10435596
JS Smith RB. Jenkins (2000) ArticleTitleGenetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications Frontiers Bioscience 5 213–231
JS Smith I Tachibana SM Passe et al. (2001) ArticleTitlePTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme J Natl Cancer Inst 93 1246–1256 Occurrence Handle10.1093/jnci/93.16.1246 Occurrence Handle11504770
JS Smith XY Wang J Qian et al. (2000) ArticleTitleAmplification of platelet-derived growth factor receptor-A (PDGFRA) gene occurs in oligodendrogliomas with grade IV anaplastic features J Neuropathol Exp Neurol 59 495–503 Occurrence Handle10850862
MT Smith CL Ludwig AD Godfrey et al. (1983) ArticleTitleGrading of oligodendrogliomas Cancer 52 2107–2114 Occurrence Handle6627218
L Sokoloff M Reivich C Kennedy et al. (1977) ArticleTitleThe [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat J Neurochem 28 897–916 Occurrence Handle864466
FJ Stott JS Bates MC James et al. (1998) ArticleTitleThe alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2 EMBO J 17 5001–5014 Occurrence Handle10.1093/emboj/17.17.5001 Occurrence Handle9724636
K Sudha AK Karak MC Sharma et al. (1998) ArticleTitleAssessment of proliferative potential of meningiomas using PCNA LI and AgNOR counts Indian J Pathol Microbiol 41 323–330 Occurrence Handle9805855
T Tanaka T Takeuchi A Nishikawa et al. (1989) ArticleTitleNucleolar organizer regions in hepatocarcinogenesis induced by N-2- fluorenylacetamide in rats: comparison with bromodeoxyuridine immunohistochemistry Jpn J Cancer Res 80 1047–1051 Occurrence Handle2514166
K Ueki Y Ono JW Henson et al. (1996) ArticleTitleCDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated Cancer Res 56 150–153 Occurrence Handle8548755
K Ueki MP Rubio V Ramesh et al. (1994) ArticleTitleMTS1/CDKN2 gene mutations are rare in primary human astrocytomas with allelic loss of chromosome 9p Hum Molec Genet 3 1841–1845 Occurrence Handle7849711
FT Vertosick SuffixJr. RG Selker SJ Grossman et al. (1994) ArticleTitleCorrelation of thallium-201 single photon emission computed tomography and survival after treatment failure in patients with glioblastoma multiforme Neurosurgery 34 396–401 Occurrence Handle8190213
MC Vigliani A Chio T Pezzulo et al. (1994) ArticleTitleProliferating cell nuclear antigen (PCNA) in low-grade astrocytomas: its prognostic significance Tumori 80 295–300 Occurrence Handle7974802
J Vion-Dury DJ Meyerhoff PJ Cozzone et al. (1994) ArticleTitleWhat might be the impact on neurology of the analysis of brain metabolism by in vivo magnetic resonance spectroscopy? J Neurol 241 354–371 Occurrence Handle7931430
H Wakimoto M Aoyagi T Nakayama et al. (1996) ArticleTitlePrognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas Cancer 77 373–380 Occurrence Handle10.1002/(SICI)1097-0142(19960115)77:2<373::AID-CNCR21>3.0.CO;2-Y Occurrence Handle8625247
Warburg O. The Metabolism of Tumors. Arnold Constable, London.
Z Zaprianov K. Christov (1988) ArticleTitleHistological grading, DNA content, cell proliferation and survival of patients with astroglial tumors Cytometry 9 380–386 Occurrence Handle2841078
P Zuber MF Hamou N. Tribolet Particlede (1988) ArticleTitleIdentification of proliferating cells in human gliomas using the monoclonal antibody Ki-67 Neurosurgery 22 364–368 Occurrence Handle2832782
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Quiñones-Hinojosa, A., Sanai, N., Smith, J.S. et al. Techniques to assess the proliferative potential of brain tumors. J Neurooncol 74, 19–30 (2005). https://doi.org/10.1007/s11060-004-5758-0
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DOI: https://doi.org/10.1007/s11060-004-5758-0