Photoreceptor differentiation in cerebellar medulloblastoma: evidence for a functional photopigment and authentic S-antigen (arrestin).

The aim of the present study was to evaluate the putative photoreceptor differentiation found in certain cerebellar medulloblastomas. The analyses were focussed on S-antigen, rod-opsin (the apoprotein of the visual pigment rhodopsin) and 11-cis retinal (the prosthetic group of rhodopsin). Fresh frozen and paraffin-embedded biopsy specimens of three medulloblastomas were investigated by means of immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), high-pressure liquid chromatography (HPLC), and immunoblotting. As shown in paraffin sections, one out of the three tumors (tumor A) contained S-antigen- and rod-opsin-immunoreactive tumor cells. The immunoblotting technique revealed in this tumor a single protein band of approximately 48-50 kDa that reacted with the S-antigen antibody and three protein bands of approximately 40, 75 and 110 kDa recognized by the rod-opsin antibody. These bands could not be detected in the two remaining tumors (tumor B and C). The rod-opsin content of tumor A was quantified by the ELISA; 11.7 pmol rod-opsin were calculated for the biopsy. The HPLC demonstrated the presence of 11-cis- and all-trans-retinal in tumor A, but not in tumors B and C. Furthermore, it was shown that 11-cis-retinal was converted to all-trans-retinal upon illumination of the tumor extract. The ratio between 11-cis- and all-trans-retinal was approximately 1:1 before illumination and 3:5 after illumination. A total of 2-3 pmol of retinal was found in the biopsy of tumor A. In addition all-trans-retinol was present in this tumor. The results indicate that certain medulloblastomas express a functional photopigment and S-antigen, another protein of the phototransduction cascade. They strongly support the concept that medulloblastoma cells may differentiate along the photoreceptor cell lineage.

Differentiation in medulloblastomas: correlation between the immunocytochemical demonstration of photoreceptor markers (S-antigen, rod-opsin) and the survival rate in 66 patients.

Biopsy specimens of 66 medulloblastomas were investigated by means of S-antigen and rod-opsin immunocytochemistry. The patients were operated between 1969 and 1988 and the medical records were retrospectively evaluated to correlate the immunocytochemical features of the tumors to the course of the disease. S-antigen- and rod-opsin-immunoreactive tumor cells were found in 19 out of 66 cases. Since in the normal non-neoplastic state immunoreactive S-antigen and rod-opsin are restricted to retinal photoreceptors and a class of pinealocytes derived from photoreceptor cells, the occurrence of these proteins in certain tumor cells of medulloblastomas suggests a differentiation of these cells along the photoreceptor cell lineage and allows the identification of a special subtype of medulloblastoma displaying photoreceptor-specific characteristics. This subtype appears to be closely related to retinoblastomas and pineal cell tumors. The incidence of this subtype corresponds to approximately 30% of all medulloblastomas. Correlation between the demonstration of immunoreactive S-antigen and rod-opsin and the course of the disease revealed a 10-year survival rate of 50.6% for patients with medulloblastomas displaying photoreceptor-specific characteristics and maximally 11% for patients suffering from medulloblastomas devoid of these markers. Although the statistical evaluation does not provide a significant result, the estimated P-value of 0.085 indicates a distinct trend toward a better prognosis for patients suffering from medulloblastomas with photoreceptor-specific features. The validity of this trend needs to be proven in further studies with a greater number of patients.

Immunocytochemical evidence of molecular photoreceptor markers in cerebellar medulloblastomas.

With the use of antisera against bovine retinal S-antigen and bovine opsin the authors demonstrate that in cerebellar medulloblastomas certain tumor cells display immunocytochemical properties characteristic of retinal photoreceptors and pinealocytes. S-antigen-like and opsin-like immunoreactions occur in nine of 28 medulloblastomas investigated. All tumors displaying S-antigen-like immunoreactive neoplastic cells also contain opsin-like immunoreactive cells; however, the opsin-like immunoreactive cells were less frequent than the S-antigen-like immunoreactive cells throughout all positive cases. The immunoreactive cells displayed several long processes. Generally, both S-antigen and opsin-like immunoreactive cells considerably vary in number among individual tumors. The results indicate that certain neoplastic cells of medulloblastoma are capable of expression of photoreceptor-specific proteins and, thus, may be closely related to tumor cells of retinoblastoma and pineocytomas previously shown to bind antisera against retinal S-antigen and opsin. No S-antigen and opsin-like immunoreaction was found in malignant teratomas and germinomas of the pineal gland, oat cell tumors, astrocytomas, ependymomas, oligodendrogliomas, glioblastomas, gangliogliomas, gangliocytoma, ganglioneuroblastomas, neuroblastomas, and esthesioneuroblastoma.