Acta Neurochirurgica 46, 53--57 (1979)
9 by Springer-Verlag 1979
Department of Neurosurgery, Neurological Institute, Faculty of Medicine, Kyushu University ':', Otsuka Assay Institute **, Fukuoka, Japan
C a r c i n o e m b r y o n i c A n t i g e n ( C E A ) L e v e l s in P a t i e n t s With Brain Tumours By E. Miyake*, M. Yamashita*, K. Kitamura*, and F. Ishi~ami**
Summary Plasma and cerebrospinal fluid CEA detemination was done in 97 patients with neurosurgical disorders. Elevated titres were found in 14 of 64 patients with brain turnouts. CEA levels were elevated significantlyin patients with metastatic brain turnouts. Following treatment, the values fell in three patients with ependymoma, medulloblastoma, and unverified brain tumour. This study suggests that CEA levels may be of value in the differential diagnosis of primary and metastatic brain tumours, and useful in the evaluation of patients with brain tumours after treatment. CEA in the cerebrospinal fluid was absent in eight patients with brain tumours.
Carcinoembryonic antigen (CEA) was first described by Gold and Freedman in 1965 6. Originally it was thought to be an antigen specific for colonic carcinoma. Subsequently this antigen has been found in association with malignancies of either endodermal or nonendodermal origin, as well as with inflammatory diseases of pancreas, liver, and colon, and with benign pulmonary diseases and chronic cigarette consumption 2, ~, 3, 5, s, 9, s0, 11, 1~, 1~, 1~ This lack of specificity indicates that CEA determination may have only limited value in early diagnosis of cancer. However, when elevated prior to treatment, subsequent serial monitoring of CEA levels has been shown to be useful in predicting the presence of occult residual tumour, and in evaluating the effectiveness of various treatments 12, 16 0001-6268/79/0046/0053/$ 01.00
E. Miyake et aL :
M a t e r i a l and M e t h o d s Sixty-four patients with brain tumours and 33 patients without turnouts as controls were studied. Of 97 patients investigated 49 were male and 48 were female subjects, ranging in age from 4 to 66. Principle of test: In this study, all CEA levels were determined on the serum with Roche Kits by Hansen Z gel assay 4, 7. Indirect assay: In brief, CEA is extracted from the plasma specimen and allowed to react with specific CEA antiserum. I=sI-CEA is then added to react with reTable 1. CEA Levels in Neurosurgical Cases CEA, ng/ml Group
No. of case
Glioma Pituitary adenoma Neurinoma Pineal tumour Craniopharyngioma Meningioma Unverified tumour Metastatic tumour Others Non-turnout
21 6 4 3 4 15 1 2 8 33
16 3 3 3 4 14 0 0 7 31
3* 1 1 0 0 1 0 0 1 2
2 2 ** 0 0 0 0 1 2 *** 0 0
* One case of Turcot syndrome. ** One case of diabetes mellitus with neuropathy and retinopathy. *** From lung cancer. maining CEA antiserum. The I~5I-CEA bound to antibody is separated from excess free I~5I-CEA with zirconyl-phosphate gel and the bound 12~I-CEA is determined by assay with gamma scintillation spectrometer. The amount of CEA present in the plasma sample is determined from a standard inhibition curve. The indirect assay quantifies the CEA content of the specimen when concentration is 20 ng/ml or less. Direct assay: When the indirect assay indicates the CEA content to be greater than 20 ng/ml, the amount can be quantified by direct assay. Specimen collection: A standard lavender-stoppered vacutainer tube containing liquid EDTA and potassium sorbate is used for the collection of 7 to 10 ml of blood. The blood is centrifuged at 1,000 G for 30 minutes. The plasma is immediately withdrawn using a Pasteur pipette, and placed in a shipping vial. This is refrigerated until the time of shipment or analysis in the laboratory. CSF is also centrifuged at 1,000 G for 30 minutes and is refrigerated.
Fourteen out of 64 patients with brain tumour showed elevation of CEA levels as shown in Table 1.
Carcinoembryonic Antigen Levels in Patients With Brain Tumours
Of 21 glioma cases, five had elevations greater than 2.5 ng/ml. Of these five cases, three were infants. The CEA level of a 4-year-old boy with a recurrent ependymoma in the fourth ventricle was 8.7 ng/ml of CEA level within 30 days postoperatively, and then fell to 2.2 ng/ml after irradiation with 4,000 rads. A 5-year-old boy with a cerebellar medulloblastoma showed a preoperative level of 3.9 ng/ml which became negative after surgery and subsequent 6~ irradiation. A 58-year-old man with an unTable 2. CEA Levels in Relation to Age Distribution of the Patients With Brain ZuFi~ours Age
CEA, ng/ml 0-2.5
0-10 10-20 > 20
5 6 39
1 0 6
2 0 5
verfied brain turnout located in the left temporal lobe, basal ganglia, and thalamus showed a CEA level of 6.1 ng/ml before treatment and of 2.2 after radiochemoimmun0therapy. The lesion in this case was taken to be a metastatic brain tumour. In two patients with metastatic brain turnout from lung cancer, CEA leves were at significant high levels (8.7 and 5.4 ng/ml). CEA levels in the CSF in the eight patients with brain tumour were negative. CEA levels of patients with pituitary adenoma were relatively high, but the cause was unknown. There was no difference in the CEA level between patients with other brain tumours and those without brain turnouts. The CEA levels of the infant patients with brain tumours seem to be higher than those of adults as shown in Table 2. Discussion
The results of this study show that 23.80/o of patients with histologically characterized glioma had CEA levels greater than 2.5 ng/mI. It has been reported that a total of 225 preoperative measurements in colorectal carcinomas, pancreatic carcinomas, metastatic breast cancers, and other turnouts showed 81, 90, 60, and 35~ incidences of elevation respectively 11. Other reports showed that the plasma
E. Miyake et al. :
levels of CEA were increased in 80~ of 49 patients with bronchiaI carcinomas and 68~ of 25 patients with an exacerbation of chronic bronchitis is. In retinoblastomas, CEA was found elevated in four of five patients is In our study, the incidence of CEA elevation in patients with primary brain tumours was lower than that in other tumours. But a significant elevation of CEA levels was observed in patients with metastatic brain tumours. The elevated CEA levels in two infants with brain tumours and an adult with an unverified brain tumour fell after treatment. These results suggest that serial CEA measurement may be of value in the differential diagnosis of brain tumours and in the evaluation of treatment of patients with brain tumours. References
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Carcinoembryonic Antigen Levels in Patients With Brain Tumours
14. Reynoso, G., Chu, T.M., Holyoke, D., Cohen, E., Nemoto, T., Wang, T.T., Chuang, J., Guinan, P., Murphy, G.P., Carcinoembryonic antigen in patients with different cancer. JAMA 220 (1972), 361--365. 15. Rieger, A., Wahren, B., CEA levels at recurrence and metastases; importance for detecting secondary disease. Scan& J. Gastroent. 10 (1975), 869--974. 16. Silverman, N. A., Alexander, J. C., Jr., Chretien, P. B., CEA levels in head and neck cancer. Cancer 37 (1976), 2204--2211. Author's address: Dr. E. Miyake, Department of Neurosurgery, Neurological Institute, Faculty of Medicine, Kyushn University, Maidashi 3-1-1, Higashiku, Fukuoka, 812 Japan.