PROLACTINOMAS EXPRESS HUMAN HEPARIN-BINDING SECRETORY TRANSFORMING GENE (HST) PROTEIN PRODUCT - MARKER OF TUMOR INVASIVENESS

BACKGROUND AND OBJECTIVE We have shown previously that heparin-binding secretory transforming gene (hst) overexpression in rat pituitary cel ls mediates lactotroph tumour growth and stimulates PRL transcription, and that transforming sequences of the gene, which encode fibroblast growth factor-4 (FGF-4), are expressed in human prolactinomas. To furt her determine the role of hst in human PRL-secreting adenoma pathogene sis we studied the presence of hst protein in these tumours and other types of human pituitary adenoma. PATIENTS AND DESIGN Pituitary adenom a tissue samples were obtained at surgery from 14 patients with PRL-se creting adenomas, 5 patients with GH-secreting tumours, 3 with ACTH-se creting, and 13 patients with nonfunctioning tumours. Two normal pitui tary tissue specimens were also studied, Clinical data, including tumo ur invasiveness assessed by preoperative MRI studies, were available. For hst protein immunolocalization, tumour frozen sections were immuno stained with antihuman FGF-4 antibody. Immunoperoxidase staining for t he proliferation-related nuclear antigen Ki-67 was performed using MIB -1 monoclonal antibody. RESULTS Normal anterior pituitary cells did no t contain immunoreactive hst protein. Lactotrophs in five of 14 prolac tinomas (36%) stained strongly for hst compared with immunoreactive pi tuicytes in only one of 21 nonfunctioning, GH-, and ACTH-secreting ade nomas (P=0.05). Immunoreactive hst in adenoma cells was detected in 3 of 5 invasive prolactinomas, and in 2 of 9 noninvasive PRL-cell adenom as. Immunostaining for the proliferation-related antigen Ki-67 showed a higher proliferation index in hst-positive adenomas (3.94 + 0.85%) a s compared with those immunonegative for hst (1.98 + 0.7%; P=0.05). CO NCLUSIONS hst protein may be directly involved in prolactinoma develop ment or progression, particularly in invasive tumours, probably due to the growth promoting effects of FGF-4.