Prolactinomas express human heparin‐binding secretory transforming gene (hst) protein product: marker of tumour invasiveness

I Shimon, DR Hinton, MH Weiss… - Clinical …, 1998 - Wiley Online Library
I Shimon, DR Hinton, MH Weiss, S Melmed
Clinical endocrinology, 1998Wiley Online Library
BACKGROUND AND OBJECTIVE We have shown previously that heparin‐binding
secretory transforming gene (hst) overexpression in rat pituitary cells 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 further determine the role of hst in human PRL‐secreting adenoma
pathogenesis we studied the presence of hst protein in these tumours and other types of …
BACKGROUND AND OBJECTIVE
We have shown previously that heparin‐binding secretory transforming gene (hst) overexpression in rat pituitary cells 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 further determine the role of hst in human PRL‐secreting adenoma pathogenesis we studied the presence of hst protein in these tumours and other types of human pituitary adenoma.
PATIENTS AND DESIGN
Pituitary adenoma tissue samples were obtained at surgery from 14 patients with PRL‐secreting adenomas, 5 patients with GH‐secreting tumours, 3 with ACTH‐secreting, and 13 patients with nonfunctioning tumours. Two normal pituitary tissue specimens were also studied. Clinical data, including tumour invasiveness assessed by preoperative MRI studies, were available. For hst protein immunolocalization, tumour frozen sections were immunostained with antihuman FGF‐4 antibody. Immunoperoxidase staining for the proliferation‐related nuclear antigen Ki‐67 was performed using MIB‐1 monoclonal antibody.
RESULTS
Normal anterior pituitary cells did not contain immunoreactive hst protein. Lactotrophs in five of 14 prolactinomas (36%) stained strongly for hst compared with immunoreactive pituicytes in only one of 21 nonfunctioning, GH‐, and ACTH‐secreting adenomas (P = 0.05). Immunoreactive hst in adenoma cells was detected in 3 of 5 invasive prolactinomas, and in 2 of 9 noninvasive PRL‐cell adenomas. Immunostaining for the proliferation‐related antigen Ki‐67 showed a higher proliferation index in hst‐positive adenomas (3.94 + 0.85%) as compared with those immunonegative for hst (1.98 + 0.7%; P = 0.05).
CONCLUSIONS
hst protein may be directly involved in prolactinoma development or progression, particularly in invasive tumours, probably due to the growth promoting effects of FGF‐4.
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