Sox9 Staining Detects Focal-Segmental Glomerulosclerosis (FSGS) in Pediatric Steroid Resistant Nephrotic Syndrome
Xu Zeng. Wayne State University, Detroit, MI
Background: In addition to minimal change disease (MCD), FSGS is an important cause of steroid resistant nephrotic syndrome in children. Under light microscopy, identification of segmental sclerosis in glomerular capillary tuft is required for the diagnosis of FSGS. Because of the "focal" nature of FSGS, the segmental sclerosis may be missed by sampling issue, therefore the diagnosis of FSGS can not be made. In addition, no reliable molecular marker for detecting FSGS is available currently. Increasing evidence indicates that FSGS is due to an irreversible podocyte damage by activation of TGF-ß mediated apoptosis and then fibrogenesis, resulting sclerosis. Sox9 is a transcriptional factor and one of the downstream targets of TGF-ß. Recent studies have been showed that Sox9 staining is positive in FSGS, but negative in MCD. Thus Sox9 can be served as a fibrogenesis marker for detecting FSGS. The purpose of this study is to evaluate the diagnostic value of Sox9 in distinguishing FSGS from MCD.
Design: Pediatric patients who had "paired-biospy", i.e. an initial biopsy with diagnosis of "MCD" then a follow-up biopsy due to sterioid resistant nephrotic syndrome with diagnosis of FSGS/MCD in Children's Hospital of Michigan during 2004-2010 were included in present study. Immunohistochemistry staining for Sox9 was performed in paraffin slide in each case. Sox9 staining (nuclear staining) in parietal epithelial cells (PEC) and podocytes were recorded as positive or negative.
Results: Seven patients had been done "paired-biopsy" in the study time frame and 4 patients had available tissue for performing immunostaining. Neither PEC nor podocyte showed Sox9 staining in initial biospy for all patients. In follow-up biospy, the Sox9 staining in podocyte is positive in FSGS patients (2/2, 100%) but negative in MCD. Sox9 staining in PEC is not detected in FSGS and MCD patient.
Conclusions: Our data indicate Sox9 staining in podocyte is valuable for evaluation of evolving MCD to FSGS and may be a useful marker to distinguishing early FSGS from MCD. Study in more cases are required to confirm the present findings.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 299, Wednesday Afternoon