oligodendroglioma: analysis 42 cases

Journal of Neurology, Neurosurgery, and Psychiatry 1987;50:304-312

Oligodendroglioma: an analysis of 42 cases

IMS WILKINSON,* JR ANDERSON,t AE HOLMES*

From the Departments of Neurological Surgery and Neurology* and Histopathology,t Addenbrooke's Hospital,Cambridge, UK

SUMMARY This paper presents the clinical and pathological data obtained from 42 patients witholigodendroglioma diagnosed over a 20 year period at Addenbrooke's Hospital, Cambridge. In allcases the diagnosis was established unequivocally by histological examination. The principalconclusions of this study were: (1) the outcome was not as favourable as anticipated, nine patientsdying within 1 year of diagnosis, and only 10 patients surviving 5 years, (2) age at the time ofdiagnosis was the single most important prognostic factor, patients under 45 years at diagnosishaving a significantly greater survival time than older patients, (3) two other factors had a

significantly adverse effect on prognosis, namely the presence of a focal neurological deficit at thetime of diagnosis and the presence of nuclear pleomorphism in the tumour when examinedhistologically, (4) although cells containing glial fibrillary acidic protein were demonstrated inalmost every tumour, their number and distribution did not appear to influence the prognosis.

Oligodendroglioma is less common than astrocytomaand generally considered to have a better prognosis,but it is also described as unpredictable with poorcorrelation between histological evidence of malig-nancy and survival.1 - 4 Its degree of prognosticuncertainty merits reassessment of its properties.Hence, the objectives of this study were two-fold,firstly to re-examine the clinical features of oligo-dendroglioma, and secondly to determine if any fac-tors, clinical, pathological or therapeutic, had asignificant influence on survival. The recently devel-oped immunoperoxidase technique for the demon-stration of glial fibrillary acidic protein (GFAP) wasincluded in the search for predictive histologicalfeatures.

Patients and methods

1. ClinicalForty-two patients with pure oligodendroglioma werediagnosed and treated at Addenbrooke's Hospital, Cam-bridge, between 1961 and 1984. The hospital records of thesepatients enabled an accurate review of the clinical features atthe time of diagnosis, of the operative findings and of thesurgical and radiotherapeutic schedules.The initial presenting symptom was recorded as epilepsy,

Address for reprint requests: Dr IMS Wilkinson, Department ofNeurological Surgery and Neurology, Addenbrooke's Hospital,Cambridge CB2 2QQ, UK.

Received 29 January 1986 and in revised form 19 April 1986.Accepted 25 April 1986

slowly evolving neurological deficit, raised intracranial pres-sure or stroke. Morbidity by the time of diagnosis was docu-mented separately. Radiological data provided evidence oftumour calcification. The surgical data provided the precisetumour location and the nature of the surgical procedure,either needle biopsy, subtotal removal or macroscopicremoval. The timing and amount of post-operative irra-diation was recorded. Finally, as almost all patients werefollowed up regularly at Addenbrooke's Hospital or withinthe East Anglian region their length of survival and status inJuly 1984 were known. Accurate follow-up has been possiblein 41 of the 42 patients, one having been lost to follow-up4 years after operation.

2. HistologyPatient selection was based on the original histology report.All the neurosurgical biopsies had been examined initially bya neuropathologist and only 42 patients with a definitereport of oligodendroglioma were included in this study.Where the histological diagnosis was in doubt or whenastrocytoma co-existed with oligodendroglioma, the patientwas excluded from the survey. In every case histologicalassessment was based on surgical material. Specimen sizevaried but all the tissue obtained by biopsy had been fixed inbuffered formal saline, paraffin embedded and sectioned forhistology.

In 1984-85 the histology of the 42 tumours was reviewedby one of us and on the basis of a haematoxylin and eosinstain all were considered acceptable as oligodendroglioma.Several morphological features were employed in a gradingsystem as detailed in table 1. The histological criteria ofmalignancy were similar to those employed in the Kernohansystem of grading astrocytomas where it has been shown tobe of prognostic significance.5`9 It was considered practicalto divide the oligodendrogliomas into only three grades.

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Oligodendroglioma. an analysis of 42 cases

Table I Oligodendroglioma-grading system

Cell density - 1/2Miloses per 10 high power fields - 1/2/3 Grade 1-3-4

(0-2, 5-9, 10+)Nuclear pleomorphism - 1/2/3 Grade 2-5-6Vascular endothelial - 0/1 Grade 3-7-10

cell proliferationNecrosis - 0/1

Histological parameters considered to be indicative of malignancywere scored on a simple point system and the total scores wereassigned to 3 grades.

Thus grade 1, expected to be the most benign, showed lowcell density, uniform nuclei, less than 2 mitoses per 10 highpower field and lacked areas of necrosis or vascular endo-thelial proliferation. Grade 3, considered the most malig-nant, showed high cell density, marked nuclear pleomor-phism, numerous mitoses and often included necrotic fociand vascular endothelial cell proliferation. Tumoursbetween these two extremes were placed in the intermediategrade 2 category. (Cell density was defined on the basis ofproximity of tumour cell nuclei, as seen in 5 pm sectionsstained with haematoxylin and eosin. In tumours of low celldensity the nuclei were at least their own width apart. Intumours of intermediate cell density the nuclei appearedalmost touching and in high density tumours they appearedto be overlapping in these sections.) Other features that wererecorded, but not incorporated into the grading system, werecalcification and the proportion showing clear cell change,that is, the classical "frog spawn" appearance of oligo-dendroglioma. The grading system was based on sectionsstained with haematoxylin and eosin. In addition alltumours were studied with the immunoperoxidase, PAPmethod, after Sternberger, to demonstrate GFAP.10 Anti-bodies used were polyclonal anti-GFAP (Dako) and swine-anti-rabbit IgG (Dako). Negative control sections wereincluded.

Results

1. Clinical.featuresThe age and sex characteristics of the 42 patients aregiven in table 2. The age at presentation ranged from7 to 69 years, with a mean of 44 years. The sex inci-dence was almost equal. The duration of the clinicalhistory and the nature of the presenting symptom are

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305shown in tables 3 and 4. Twenty-two patients gave ahistory longer than one year. Of the 19 patients whosefirst symptom was epilepsy, 15 gave a history longerthan one year, nine more than 5 years. Of the 23patients whose first symptom was something otherthan epilepsy, such as raised intracranial pressure orfocal neurological deficit, 16 gave a history of lessthan one year's duration. The first symptom wasgrand mal epilepsy in 13 patients, focal epilepsy in sixpatients, clinical evidence of raised intracranial pres-sure in 13 patients, the gradual evolution of a focalneurological deficit in seven patients and suddenonset of focal neurological deficit (stroke-like) in

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Table 3 The number ofpatients showing each of thefivepresenting symptoms.

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Table 4 The duration of the clinical history in the wholegroup ofpatients; (a) in patients whose presenting symptomwas epilepsy; and (b) in patients whose presenting symptomwas something other than epilepsy (c).

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Table 2 The age and sex characteristics of the patients atthe time ofdiagnosis.

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three. In the stroke-like presentations the clinical pic-ture was of recurrent transient ischaemic attacks inone instance, of cerebral infarction in another and offatal intracerebral haemorrhage in the third.Although table 3 illustrates the first symptom of eachpatient, it is important to note that by the time ofdiagnosis 24 of the 42 patients had suffered epilepticattacks, 25 had clinical evidence of raised intracranialpressure and 25 had localising neurological signsappropriate to the site of the lesion.

Figure 1 shows the anatomical location of thetumours. The frontal predominance is noteworthy.Twenty-two tumours involved the right cerebralhemisphere, 16 the left and four were midline,involving both cerebral hemispheres. There were noinfratentorial tumours in this series. Figure 2endeavours to show the relationship between thenature of the first symptom and tumour site. How-ever, the nature of the first symptom did not showgood correlation with the intracerebral location withthe possible exception of tumours situated in thefronto-temporal or temporal region, of which seven

Fig 1 A diagram to show the location of the 42 tumours.

Wilkinson, Anderson, Holmes

out of nine presented with epilepsy as their first symp-tom.

Calcification of the tumour was diagnosed pre-operatively in 21 (50%) patients, in 18 of 36 who hadskull radiographs and in 12 of 24 who had a CT scan,(some patients had both investigations).The surgical treatment was biopsy only in 10 cases,

subtotal removal in 18 and macroscopic removal in14 patients. Thirty-eight patients had a full course ofradiotherapy immediately post-operatively, consis-ting of between 4,000 and 4,950 rad administered in15 to 20 fractions. Three patients declined very rap-idly after their surgical treatment and were never ableto undergo a full course of radiotherapy. One patientdid not receive radiotherapy after the initial surgery,but it was given with benefit 18 months later fortumour recurrence. Thus in this series there is onlyone patient who has survived for several years whodid not receive early radiotherapy. The majority ofpatients in this survey received practically the samemanagement, a major surgical resection followed byradiotherapy. *r, > ;-0/

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Fig 2 A diagram to show the relationship betweenpresenting symptom and tumour location.

Fig 3 (a) Example ofoligodendroglioma Grade 1, showinglow cell density, small, uniform nuclei and absence ofmitoticactivity (haematoxylin and eosin x 50) (b) Large GFAPpositive cells, with astrocytic morphology, amongst smallernegative tumour cells. (Same tumour as (a))(immunoperoxidase methodfor GFAP x 50).



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At the time of data collection in July 1984 the out-come of treatment was known in 41 of the 42 patients.The one remaining patient was lost to follow-up 4years after operation. The median survival time was44 months and only 14 patients were known to bealive in July 1984. Ten patients had survived for 5years or more, the longest survivor remaining aliveand well 17 years after treatment. Nine of the patientshad died within a year of treatment, one as a result ofpulmonary embolism, but as a direct result of thetumour in the other eight.

2. HistologicalfindingsRe-assessment of the original haematoxylin and eosinstained sections in 1984 confirmed the original diag-nosis of oligodendroglioma. In two cases only, thepossibility of an astrocytomatous component wasqueried at this stage, but because of a definite prepon-derance of distinctly oligodendrogliomatous tissuethese cases were retained. Histological grading, (as setout in table I and illustrated in fig 3a, 4a and 5a)

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Fig 4 (a) Example ofoligodendroglioma Grade 2, showingmoderate nuclear pleomorphism and occasional mitoticfigures. (haematoxylin and eosin x 50) (b) Scattered smalltumour cells show positive reaction for GFAP(immunoperoxidase method.for GFAP x 50) (same tumour

as (a)).

307

assigned 11 tumours to grade 1, seven to grade 2 andthe majority, 24 tumours to grade 3. The biopsieswere frequently non-uniform (14/42 cases). Foci oflow cell density with regular rounded small nuclei co-existed with areas showing obvious nuclear pleomor-phism. Large areas of clear cell change correlated bestwith low grade tumours, although two grade Itumours did not contain any such foci. These wereexamples of oligodendroglioma formed of cells withabundant eosinphilic cytoplasm and slightly eccentricnuclei, a well recognised appearance.

Calcification was detected in 15 tumours, in theform of calcospherities of variable density. Occa-sionally the calcification appeared greatest in the nontumourous tissue at the edge of the biopsy. Histologi-cal evidence of calcification did not correlate very clo-sely with the radiological findings. Although in 25/42cases there was agreement on either positive or nega-tive findings, there was a discrepancy in 15 cases(radiological data were not available in two cases). Ineight of these 15 cases calcification was only detected

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Fig 5 (a) Example of oligodendroglioma Grade 3, showinghigh cell density, severe nuclear pleomorphism andftequentmitoses. (Haematoxylin and eosin x SO) (b) Many of thetumour cells are GFAP positive. There is variation in cell sizeand shape, but the larger cells do not have typical morphologyoffibrous astrocytes. (immunoperoxidase methodfor GFAPx 50) (same tumour as (a)).



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by radiology and in the other seven only by histology.Cells staining positively for GFAP were detected in

almost every tumour (figs 3b, 4b and 5b). (Reserveparaffin embedded tissue was not available in onecase). Several distinctive patterns emerged. Largebiopsies with non-uniform histology frequentlyexhibited more than one pattern. The staining reac-tions are illustrated diagrammatically in fig 6.

In patterns 1 and 2 the large cells with long pro-

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cesses were interpreted as reactive astrocytes, becausethey appeared to be a completely different populationfrom the small rounded tumour cells with notransitional forms and also because identical patternscan be seen in non-glial neoplasms, such as malignantcerebral lymphoma. The astrocytic network patternwas particularly characteristic of the grade I tumour,present in all but 1/11 tumours. However the findingof reactive astrocytes within the tumour was not

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Fig 6 Diagrams to summarise the appearance and distribution ofGFAP positive cells inoligodendrogliomas. Positive cells are indicated by dark cytoplasm:(0) Large areas of tumour are completely negative(I) Positive cells are present at the periphery of the tumour and are larger than the majority ofunstainedtumour cells. The positive cells have long cytoplasmic processes suggesting they arefibrous astrocytes.(2) Positive cells, resemblingfibrous astrocytes, are dispersed in a network pattern amongst smallerunstained tumour cells, as shown infig 3b.(3) Positive cells arefew in number, but are the same size and shape as unstained small tumour cells.(4) Positive cells have the same morphology as pattern 3, but the majority oftumour cells are stained, asshown infigs 4b and 5b.(5) Large astrocyte-like and smaller tumour cells are both positive with transitional forms.

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confined to low grade neoplasm and was also present assessed bin several of the more pleomorphic high grade the life tattumours. In patterns 3 and 4 the positive cells were the log rainterpretated as neoplastic cells because they were relations hmorphologically indistinguishable from unstained by this metumour cells. This cell type has been recognised by aged 45 yother investigators and labelled glial fibrillary oligo- patients ledendrocyte, (GFOC), by one." This staining pattern whole groiwas seen in one grade I tumour and in several inter- The bettermediate and high grade tumours (figures 4b and Sb). with the

00001).3. Factors predicting outcome Of the oFactors which might have predictive value were sis, the on

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309iy the use of survival curves, calculated bybe method, which were compared by usingank test.12 13 Statistically significant cor-ave been achieved in this group of patientsthod. In fig 7 the survival curve of patients'ears and over is compared with that ofEss than 45 years, (the mean age for theLup at the time of diagnosis was 44 years).r survival of the younger group comparedolder patients is highly significant (p =

ther clinical features at the time of diagno--ly factor to achieve statistical significance

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Fig 7 Survival curves to show the predictive value ofage at the time ofpresentation.

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Fig 8 Survival curves to show the predictive value ofthe presence ofafocalneurological deficit at the time ofpresentation.

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Fig 9 Survival curves to show the predictive value ofthe presence ofnuclearpleomorphism in the tumour.

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310was the presence of focal neurological deficit at thetime of presentation. Figure 8 shows the difference insurvival between those with, and those without such adeficit. This difference is statistically significant, (p =0-0242). Of the histological features of the tissueremoved at the time of diagnosis, nuclear pleomor-phism was the single characteristic to show a statisti-cally significant correlation with survival, (p =

0-0127), as shown in fig 9.Other factors which showed trends by this method

of analysis, but which did not achieve statisticalsignificance, include the duration of symptoms priorto diagnosis, radiological evidence of calcification,mitotic activity in the tumour and its overall histolog-ical grade. Patients with a long history, with acalcified tumour, with low mitotic rates and low histo-gical grade fared better, but the trends in the survivalcurves did not achieve statistical significance for thesefactors.

Trends for other clinical, treatment and histologi-cal characteristics were sought but not found. Hence,there was no demonstrable correlation between sur-

vival time and the following clinical features; sex,

nature of the first symptom, occurrence of epilepsy,raised intracranial pressure or location of the tumour.The different surgical procedures did not produce any

significant differences in survival time and there was

equally negative correlation with the following histo-logical features; necrosis, vascular endothelial cellproliferation, clear cell change and the variouspatterns of GFAP containing cells in the tumour.

Discussion

Analysis of the comprehensive data collected fromthese patients has clarified the common clinicalfeatures of oligodendrogliomas and has revealedcertain clinical and pathological factors of prognosticsignificance. Following a brief preliminary commu-

nication,'4 the results are now discussed in detail.In the first category this series has emphasised that

oligodendrogliomas are tumours of the cerebralhemispheres in adults. The fact that over 20 years in aregional neurosurgical centre only one oligodendro-glioma has been diagnosed in childhood has con-firmed their rarity in this age group. Likewise, sub-tentorial oligodendrogliomas are unusual and therewere none in this group. A frequent frontal locationhas been confirmed. A long preceding history of epi-lepsy and radiological tumour calcification are alsocommon. It must be emphasised however that half thepatients in this study gave a history of less than a year,half the patients did not present with epilepsy as theirinitial symptom, and half the patients showed nocalcification of their tumour on skull radiographs orCT scan. Clearly diagnostic thoughts of oligodendro-

Wilkinson, Anderson, Holmesglioma cannot be confined to patients with a calcifiedlesion presenting with a long history of epilepsy.

In the second category, the first observation mustbe the rather poor overall prognosis for patients witholigodendroglioma. Whilst comparing well with theprognosis for patients with grade 3 and 4 astro-cytomas,' 5 the outlook for patients with oligodendro-glioma in this series was only fair, (9/42 patients,21%, dying within 1 year and only 10/42 patients,24%, surviving 5 years from the time of diagnosis andtreatment). This outcome is similar to several reportson survival in the literature, but not as satisfactory asthe figures produced by Smith et al, 48% 5 yearsurvival'6 and by Chin et al, 60% 5 year survival.3

Previous workers have had difficulty in establishingany clinical factors which have correlated reliablywith prognosis. The unpredictability of oligo-dendroglioma is a feature of many reports. In thisstudy, age at the time of diagnosis has been shown tobe an overriding and statistically significant factor. Inthis fairly small series it is not possible to determinewhether the adverse effect of age is solely due to theinability of older patients to withstand the presence ofa brain tumour and the effects of anaesthesia andmajor surgery, or whether there is a genuinedifference in the biological behaviour of the tumours.Even if it is not the only factor, it seems likely thatcomparatively poorer general health must to someextent be responsible for the more rapid demise of theolder patients. If so, even more rigorous attention topre-operative and post-operative care may increasethe survival in this group. In this series, eight patientsfrom the older group died within the first few post-operative weeks, (one from pulmonary embolus, butthe rest from the direct effects of their brain tumour).All of the younger patients survived the post-operative period and the earliest death in this groupwas at 1 year. The series is too small to prove asignificant biological difference in the tumours ofolder patients, but it is of interest that the majority ofgrade I tumours, eight out of I1, were identified in theyounger patients.The statistically significant correlation of poor

prognosis with the presence of a focal neurologicaldeficit at the time of diagnosis has not been reportedpreviously and, along with age, becomes one of thetwo useful clinical factors to remember when coun-selling patients with oligodendriglioma and theirrelatives.The value of histological grading has long been a

source of controversy in oligodendroglioma. Smith etal have advocated grading and have shown a cor-relation between histological features and survival,'6whereas others have claimed histology was irrele-vant. 1 2 In this series there is a definite trend shown inthe survival curve for grade I and grade 2 tumours to



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Oligodendroglioma. an analysis of 42 cases

fare better than grade 3. This did not achieve statisti-cal significance but this is probably because the num-bers in each group were too small. However, as in aprevious survey, nuclear pleomorphism alone hasproved to be a significant prognostic factor. Thetumours were graded as in the Kernohan system forastrocytomas with the additional refinement of apoint scoring system, and grade 3 and 4 tumours wereincluded in a single category. The majority ofneuropathologists employ this system for astro-cytomas and at present we would advocate its appli-cation to oligodendrogliomas, whilst accepting thatas more oligodendrogliomas are assessed, differentweighting may be needed for individual morphologiccriteria.

Immunoperoxidase staining for GFAP was per-formed in the hope of identifying new histologicalprognostic factors. This hope was not fulfilled. Cellsinterpreted as reactive astrocytes were found in bothlow grade and high grade tumours and their presenceshowed no correlation with survival. However, thismethod may yet prove useful to distinguish differenttypes of oligodendroglioma and to segregate mixedtumours, that is tumours which are partly oligo-dendrogliomatous, but also contain neoplastic astro-cytes. Tumours in which the two malignant com-ponents are quite separate are generally recognisablewith haematoxylin and eosin. Tumours of this typewere excluded from this series. However there doesappear to be a category, particularly well demon-strated by GFAP, with a spectrum of positive cellsfrom small round oligodendrocyte like cells to largepleomorphic cells with astrocytic morphology. Therewere only two tumours in this category, both classedas grade 3. It may be anticipated that these willbehave as malignant astrocytomas, but more data arerequired. Until a reliable and specific immunologicalmarker for oligodendrocytes is found, the inclusion ofGFAP staining in the histological assessment ofoligodendrogliomas will help to eliminate mixedtumours from any survey and thus assist recognitionof comparable tumours for inclusion in therapeutictrials.The identification of GFAP in well differentiated

oligodendrogliomas is at first surprising as it isgenerally regarded as a marker of astrocyticdifferentiation. However, a recent study of developingmyelin suggests that GFAP is expressed transiently indeveloping oligodendrocytes. 7 If this is confirmed, inthis situation GFAP can be regarded as anotheroncofetal antigen.

Despite the large volume of data collected from amajor neurosurgical centre the number of patients istoo small for significant results to be obtained from amultivariate analysis; nevertheless certain trends haveemerged which indicate the need for further detailed

311

documentation of oligodendroglioma. On presentevidence it seems that the general optimism whichgreets diagnosis of oligodendroglioma, as opposed tomalignant astrocytoma, is justified, provided thepatient is a young adult. In this series young age out-weighed histological evidence of malignancy. Theprognosis of all grades of oligodendroglioma inyoung adults is far better than that for grade 3 and 4astrocytoma. Likewise benign histology in an olderpatient does not guarantee a favourable outcome andin the older group the prognosis, whilst not as poor,approaches that of high grade astrocytoma.

We thank, most sincerely, Dr Lawrence Freedman forhis very considerable help in the statistical analysespresented in this paper.

References

I Russell DS, Rubenstein LJ. Oligodendroglioma. In:Pathology of Tumours of the Nervous System. London.Edward Arnold Ltd 1977:195-203.

2 Roberts M, German WJ. A long term study of patientswith oligodendrogliomas. J Neurosurg 1966;24:697-700.

3 Chin HW, Hazel JJ, Kim TH, Webster JH.Oligodendrogliomas. Cancer 1980;45: 1458-66.

4 Reedy DP, Bay JW, Hahn JF. Role of irradiation ther-apy in the treatment of cerebral oligodendroglioma:an analysis of 57 cases and a literature review.Neurosurgery 1983;13:499-503.

5 Kernohan JW, Sayre GP. Tumours of the central ner-vous system. In: Atlas of Tumour Pathology, section10 fascicles 35 and 37. Washington DC, Armed ForcesInstitute of Pathology, 1952.

6 Burger PC, Vollmer RT. Histologic features of prognos-tic significance in the glioblastoma multiforme. Cancer1980;46:1179-86.

7 Nelson JS, Scheonfeld D, Tsukada Y, Fulling K. Histo-logic criteria with prognostic significance for malignantglioma. In: Chang CH, Housepian EM, eds. Tumoursof the Central Nervous System. New York: MassonPublishing, 1982:1-4.

8 Byar DP, Green SB, Strike TA. Prognostic factors formalignant glioma. In: Walker MD, ed. Oncology of theNervous System. The Hague. Martinus Ni.ihoff1983:397-5.

9 Chang CH, Horton J, Schenfeld D, et al. Comparison ofpostoperative and combined postoperative radio-therapy and chemotherapy in the multidisciplinarymanagement of malignant gliomas. Cancer1983;52:997-1007.

10 Sternberger LA. The unlabelled antibody peroxidase-antiperoxidase (PAP) method. In: Immunocyto-chemistry. New York: John Wiley 1979:104-70.

11 Herpers MJHM, Budka H. Glial fibrillary acidic protein(GFAP) in oligodendroglial tumours: gliofibrillary oli-godendroglioma and transitional oligoastrocytoma assubtypes of oligodendroglioma. Acta Neuropathol(Berl) 1984;64:265-72.



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12 Kaplan EL, Meier PJ. Non-parametric estimation fromincomplete observations. J Am Statistical Association1958;53:457-8 1.

13 Peto R, Pike MC, Armitage P. Design and analysis ofrandomised trials requiring prolonged observation ofeach patient. 2. Analysis and examples. Br J Cancer1 977;35: 1-39.

14 Anderson JR, Wilkinson IMS, Holmes AE.Oligodendroglioma-a clinicopathological study of 40cases diagnosed in a 20 year period. Neuropathol AppiNeurobiol 1985;1 1:505-6.


15 MRC. Working Party on Misonidazole in Gliomas. Astudy of the effect of Misonidazole in conjunction withradiotherapy in the treatment of grades 3 and 4 astro-cytomas. Br J Radiol 1983;56:673-82.

16 Smith MT, Ludwig CL, Godfrey AD, ArmbrustmacherVW. Grading of oligodendrogliomas. Cancer1983;52:2107-14.

17 Choi BH, Kim RC. Expression of glial fibrillary acidicprotein in immature oligodendroglia. Sc ience1984;223:407-9.



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