title: Immunohistochemical evaluation of the post-translational processing of chromogranin A in human pituitary adenomas.
abstract: Chromogranin A (CgA), pancreastatin (PST), intervening-peptide (IP) and WE-14 antisera were employed to investigate the proteolysis of CgA in 50 pituitary adenomas. All non-functioning (NF) pituitary tumours (n = 28) exhibited CgA immunoreactivity. PST, IP and WE-14 immunostaining was observed in 85%, 89% and 67%, respectively. CgA, PST and IP immunostaining were comparable in the majority of NF tumours, while less intense WE-14 immunoreactivity was detected in a subpopulation of NF tumour cells. Approximately half of the functioning pituitary tumours expressed CgA immunoreactivity. Six of nine ACTH-secreting tumours displayed CgA and IP immunostaining; four of these tumours displayed PST immunoreactivity. WE-14 immunoreactivity was detected in one corticotroph tumour. Three of six growth hormone (GH) secreting tumours displayed CgA immunostaining, two exhibited PST and IP, and one exhibited WE-14 immunoreactivity. Clusters of WE-14 immunopositive cells were detected in one GH tumour. One of seven prolactinomas exhibited weak CgA immunostaining, while weak IP and WE-14 immunostaining was detected in an additional tumour. No PST immunostaining was detected in prolactinomas. Therefore CgA is a valuable marker of NF pituitary tumours, however it is a more sporadic marker of functioning adenomas. In general, the cellular pattern and intensities of CgA, PST and IP immunoreactivity were comparable in the majority of pituitary adenomas. In contrast, WE-14 immunostaining was observed in a subpopulation of tumour cells. The pathophysiological significance of the proteolysis of CgA to generate bioactive peptides in both NF and functioning pituitary adenomas remains to be established.
authors.affiliation: Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, Northern Ireland.
authors.forename: A P
authors.initials: AP
authors.lastname: Heaney
authors.forename: W J
authors.initials: WJ
authors.lastname: Curry
authors.forename: K M
authors.initials: KM
authors.lastname: Pogue
authors.forename: V L
authors.initials: VL
authors.lastname: Armstrong
authors.forename: M
authors.initials: M
authors.lastname: Mirakhur
authors.forename: B
authors.initials: B
authors.lastname: Sheridan
authors.forename: C F
authors.initials: CF
authors.lastname: Johnston
authors.forename: K D
authors.initials: KD
authors.lastname: Buchanan
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
mesh_terms: D000236:Adenoma / Q000097:blood / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010907:Pituitary Hormones / Q000097:blood; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D010907:Pituitary Hormones; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone