The aim of the present study was to compare the expression levels of
secretogranin II (SgII),
prohormone convertases (PC)1 and PC2, and the proteolytic processing of SgII in benign versus malignant
pheochromocytomas. Quantitative (Q)-PCR experiments indicated that SgII, PC1, and PC2 mRNAs were overexpressed in
pheochromocytoma compared to non-tumoral chromaffin cells (P<0.001) and in benign compared to malignant
tumors (P<0.01). Western blot analysis using a human SgII antiserum revealed the occurrence of a 97-kDa band corresponding to the expected size of SgII, with significantly higher quantities in benign than in malignant
tumors (P<0.05). Using
antisera directed against sequential regions of SgII (N-terminal,
secretoneurin [SN], EM66, internal, and C-terminal sequences), we observed distinct processing profiles between benign and malignant
pheochromocytomas. In contrast, using PC1 and PC2
antisera no differences between the two types of
tumors were found. RIA measurement showed that EM66 median values between benign and malignant chromaffin cell
tumors were significantly different (128.5 vs. 6.3 ng/mg
protein, respectively; P<0.001). Taken together, these results indicate that, in
pheochromocytoma,
malignancy is associated with reduced PC1, PC2, and SgII
mRNA expression and decreased levels of processing products of SgII, in line with the low concentrations of EM66 that occur in malignant
tumors. These data support the notion that SgII-processing products, such as EM66, could represent prognostic markers of
pheochromocytomas.