IMMUNOHISTOCHEMICAL DETECTION OF HUMAN NATURAL-KILLER-CELL LIKE IMMUNOREACTIVITY IN HUMAN PITUITARY-ADENOMAS, USING MONOCLONAL-ANTIBODY NK-1

Natural killer (NK) cells are specialized lymphocytes which are charac terized as non-T and non-B cells, as they lack classic T and B cell su rface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived fro m the neuroectoderm and neuroendocrine system. We examined the express ion of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing a denomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) pr oducing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immune-endocrine mod ulators, were also examined. In normal pituitary glands, NK-1 was dete cted in all 6 tissues in the cytoplasm of about 5-10 % of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH, PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimu lating hormone (FSH beta), TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pit uitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adeno ma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL prod ucing adenomas (50%), 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfuctioning adenomas (31.3%). By double immunostaining, NK-1 was found to be frequently colocalized with ACTH in ACTH producing adenomas, and was colocalized with PRL in PRL producing adenomas, or with GH, PRL or the alpha-subunit in GH pr oducing adenoma cells. NK-1 immunoreactive cells were observed in clos e association with S-100 immunopositive FS cells in the adenomas. Our results may indicate that NK-1 positive cells may have functions as a paracrine modulators of their neighboring cells, which includes S-100 positive FS cells.