Immunoreactive S-antigen in cerebrospinal fluid: a marker of pineal parenchymal tumors?

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✓ This investigation evaluated the possibility that the occurrence of S-antigen in cerebrospinal fluid (CSF) might be used as a preoperative marker of pineal parenchymal tumors (pineoblastoma and pineocytoma). Such a marker could provide a means of preoperatively differentiating these neoplasms from pineal region tumors of other origin. The S-antigen, also known as the 48-kD protein or arrestin, is a highly antigenic protein originally found in the retina and pineal gland. In the retinal photoreceptors and submammalian pineal photoreceptors the protein is thought to be involved in phototransduction; its function in the mammalian pinealocyte is unknown. S-Antigen immunoreactivity also occurs in certain neoplastic cells of retinoblastomas, pineocytomas, pineoblastomas, and cerebellar medulloblastomas. This study included a group of 13 patients with tumors of the pineal region. Samples of CSF were obtained preoperatively and analyzed for the S-antigen using western blot technology. Tumor biopsy material was classified according to conventional neurohistological criteria and was also examined by immunocytochemical techniques for the presence of the S-antigen. S-Antigen immunoreactivity was found in the preoperative CSF of the one patient found to have pineocytoma; tumor tissue removed from this patient was the only neoplastic tissue examined in this study which contained S-antigen immunoreactive tumor cells. Furthermore, hydroxyindole-O-methyltransferase activity was detectable in the pineocytoma but not in three other pineal tumors, and melatonin levels in the CSF of the pineocytoma patient were the highest in the patient group examined. These preliminary results suggest that testing for S-antigen in CSF might be useful in characterizing and treating tumors of the pineal region and, when identified in conjunction with other markers, it might also help to better define pineal parenchymal tumors. This study needs confirmation with a larger number of patients. If this approach is eventually found to be a reliable predictor of pineal cell tumors, it may supplant the need for surgical biopsies before initiating appropriate adjunctive therapy.

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Address reprint requests to: David C. Klein, Ph.D., National Institutes of Health, 10/8D42C, Bethesda, Maryland 20892.

Address for Dr. Korf: Department of Anatomy and Cytobiology, Justus Liebig University of Giessen, Aulweg 123, D-6300 Giessen, Federal Republic of Germany.

© AANS, except where prohibited by US copyright law.

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    Immunoblots of 10% SDS-PAGE of proteins in cerebrospinal fluid (CSF) and tumor homogenates. For the CSF studies (Lanes A-F), 40 µl CSF was applied to each lane. Image enhancement was used to produce the contrast required for reproduction. Lane A: Immunoreactive band of approximately 48- to 50-kD molecular weight (MW) detected in the CSF of Case 3 by use of whole antiserum NEI-04111083. Lanes B, C, and D: Western blot analysis of CSF from Cases 1,2, and 6. Following incubation with whole antiserum NEI-04111083, no immunoreactive protein band was detected. Lane E: Immunoreactive band of approximately 48- to 50-kD MW detected in Case 3 by use of immunopurified antibody. Lane F: After preadsorption of the antiserum with purified S-antigen, this band is no longer detectable. Lanes G, H, and I: Western blots of tumor homogenates of Cases 3, 1, and 2, respectively, incubated with purified S-antigen antibody. An immunoreactive band of approximately 48- to 50-kD MW was detected only in the tumor homogenate of Case 3.

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    Immunocytochemical demonstration of S-antigen immunoreactive tumor cells in the pineocytoma from Case 3 and in normal pineal tissue from Case 8. × 300 (bars = 30 µM). a: Case 3. S-antigen-immunoreactive tumor cells of the pineocytoma (arrowheads) are scattered between immunonegative tumor cells. Arrows indicate beaded processes. b: Case 3. No immunoreactive cells are found in an adjacent section, incubated with the preadsorbed antibody. c: Case 8. Normal S-antigen immunoreactive pinealocytes (arrowheads) give rise to beaded processes (arrows).

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