Immunohistochemical expression of chromogranins A and B, prohormone convertases 2 and 3, and amidating enzyme in carcinoid tumors and pancreatic endocrine tumors.
Although chromogranin A (CgA) is widely distributed in neuroendocrine tumors, the distribution of chromogranin B (CgB) has not been elucidated. Hormones produced by tumors are sometimes prohormones and not necessarily bioactive hormones. Prohormones have to be processed into bioactive peptides by prohormone convertases (PCs), and some of them have to be amidated by peptidylglycine a-amidating monooxygenase (PGM). Whether PCs and PGM are present or not in tumors may explain why some tumors are functioning and some are nonfunctioning. We investigated 45 carcinoids and 16 pancreatic endocrine tumors. Of the carcinoids, CgA was expressed in most of the tumors, except for the rectal and ovarian carcinoids, which expressed CgB strongly. The expressions of PC2, PC3, and PGM were 31%, 100%, and 87%, respectively. In the pancreatic tumors, CgA was expressed in all tumors, whereas CgB was not expressed in any tumor. The expressions of PC2, PC3, and PGM were 63%, 88%, and 63%, respectively. PC3 was expressed in all of the functioning tumors but not in two of the four nonfunctioning tumors. PC2 and PGM were not expressed in three of the four nonfunctioning tumors. In conclusion, expression of CgA and CgB was different depending on the tumor location. High frequency of PCs and PGM may explain why even nonfunctioning tumors produce some inconspicuous peptides.
Kimura
N
N
Department of Pathology, Tohoku University School of Medicine, Tohoku Rosai Hospital, Sendai, Japan. nkimura@patholo2.med.tohoku.ac.jp
Pilichowska
M
M
Okamoto
H
H
Kimura
I
I
Aunis
D
D
D007516:Adenoma, Islet Cell / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis; D003480:Cushing Syndrome / Q000378:metabolism / Q000473:pathology; D015408:Gastrinoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D051381:Rats; D013381:Subtilisins / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases