Histological features and expression of enzymes implicated in melatonin synthesis in pineal parenchymal tumours and in cultured tumoural pineal cells.

Pineal parenchymal tumours (PPT) are rare neoplasms and there have been few in vitro studies. Their capacity for synthesizing and secreting melatonin has been only partially examined. We investigated the presence of messenger RNA (mRNA) encoding tryptophan hydroxylase (TPH), arylalkylamine N-acetyltransferase (AANAT), hydroxyindol-O-methyltransferase (HIOMT), three enzymes involved in melatonin synthesis, and c-myc, a tumoural marker, in 10 PPT, one papillary tumour of the pineal region (PTPR), cell cultures derived from four PPTs and from three other tumours of the pineal region, and in normal pineal gland. Moreover, protein expression of TPH was investigated in three PPT and PTPR. Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry were used and the melatonin production by tumoural cells in vitro was analysed by radioimmunoassay. We showed that all the tumoural tissues and cells contained c-myc mRNA. mRNAs encoding TPH, AANAT and HIOMT were detected in all PPT, suggesting that tumour cells can synthesize melatonin. Only PPT expressed TPH protein. Cultured cells lost expression of transcripts throughout passages even if ultrastructural study revealed the presence of characteristic organelles in these tumoural cells. Nevertheless, the basal secretion of melatonin observed in one PPT culture is in favour of a maintained melatonin production and secretion by tumoural pinealocytes, but melatonin production was not stimulated by a beta noradrenergic agonist. Moreover, PTPR never expressed mRNA encoding TPH, AANAT and HIOMT. Our results may contribute to a better understanding of the biology of PTT and PTPR and may help to the diagnosis of these rare tumours.

Calcineurin, a calcium/calmodulin-regulated protein phosphatase, in mammalian neuroendocrine cells and neoplasms.

Calcineurin is a calcium/calmodulin-regulated protein phosphatase. By using enzyme-immunoassay and immunocytochemistry with an affinity-purified specific antibody to this protein, we have found that calcineurin is expressed in the central and peripheral neuroendocrine cells, also termed amine precursor uptake and decarboxylation cells. In addition, calcineurin immunoreactivity was found in the central neuroendocrine neoplasms such as pineocytoma, olfactory neuroblastoma and paraganglioma. The present findings indicate that the activity of phosphatase regulated by calcium and calmodulin is involved in neuroendocrine functions, and that the enzyme can be useful for the identification and characterization of neuroendocrine cell tumors.

Cerebrospinal fluid placental alkaline phosphatase in the intracranial germinomas: results of enzyme antigen immunoassay.

The authors investigated the placental alkaline phosphatase (PALP) activity in cerebrospinal fluid (CSF) by enzyme-antigen immunoassay using polyclonal antibody as a marker for intracranial germinomas in 17 patients with germ cell tumors and 20 with other disorders. The detection limit of PALP activity was 0.072 optical density units equivalent to 5.9 ng/ml. Five of nine germinomas demonstrated high CSF PALP activities before treatment. These high PALP activities became undetectable following radiation therapy. The other tumors were small or had no CSF contact. CSF PALP activity is a useful tumor marker for pure germinomas.

Pathological survey of intracranial germinoma and pinealoma in Japan.

Pathologic survey was performed on 43 cases of intracranial germinoma and 12 cases of pinealoma. The present study suggests that, in Japan, the incidence of teratoma groups including germinoma is remarkably higher than that in U.S. and Europe, whereas the rate of true pinealoma is lower. Using ultrastructural, enzyme-histochemical, and fluorescence-histochemical methods for a few surgical specimens, a strong similarity between intracranial germinoma (so-called "pinealoma" with a two-cell pattern) and seminoma and dysgerminoma was confirmed. The true pinealoma could be classified as pineoblastoma and pineocytoma, according to the degree of pineocyte differentiation of the tumor cells, and as "neuroblastoma-like" and "pineal-like" on the basis of the histologic architecture.

Modification of hydroxyindole-O-methyltransferase activity in experimental pineocytomas induced in hamsters by a human papovavirus (JC).

Hydroxyindole-O-methyltransferase (HIOMT) (HIOMT) activity was studied and compared in 7 pineal tumors (pineocytomas) induced in vivo in Syrian hamsters after postnatal inoculation with strains of human papovavirus (JC). Levels of tumor HIOMT activity were correlated with degree of cytologic differentiation of the pineocytes of each neoplasm, as judged from electrom micrographs. The relative capacities of the HIOMT in the tumors to methylate three related substrates gave similar ratios in the individual tumors and were not different from those of HIOMT in normal hamster pineal glands.

Ectopic pinealoma: an unusual clinical presentation and a histochemical comparison with a seminoma of the testis.

A patient with ectopic pinealoma first presented with apparent anorexia nervosa and hypernatraemic coma. A history of diabetes insipidus two months previously was not known on admission to hospital. The diabetes insipidus was unmasked by the administration of steroids. Neuroendocrinal and neuropathological aspects of the case are discussed with reference to the march of symptoms due to the growth of the tumour. Histochemical evidence is presented supporting the similarity between ectopic pinealoma and seminoma which suggests that they may more properly be referred to as atypical teratomas.