Dystroglycan in the diagnosis of FSGS.
OBJECTIVE
alpha- and beta-dystroglycan (DG), which link the actin cytoskeleton of the podocyte to the glomerular basement membrane, are maintained in FSGS but decreased in minimal change disease (MCD). Fibrosis has been linked to increased fibroblast-specific protein-1 (FSP1) and epithelial-mesenchymal transition. We studied DG, FSP1, and podocyte differentiation in FSGS variants and cases of suspected FSGS.


METHODS
We studied renal biopsies with FSGS, not otherwise specified (NOS), tip lesion, or collapsing variants (COLL), versus secondary FSGS or cases without segmental sclerotic lesions where a diagnosis of MCD versus FSGS could not be established (undefined [UNDEF]) and compared the expression of DG, FSP1, and podocyte Wilms' tumor antigen (WT1).


RESULTS
WT1 is markedly decreased in NOS versus normal and correlates with the extent of sclerosis. alpha- and beta-DG are maintained in most primary and secondary FSGS cases. In contrast, alpha-DG is significantly decreased in UNDEF, supporting a diagnosis of MCD. Furthermore, follow-up shows remission or decreased proteinuria in four of six of these UNDEF cases in response to therapy. Interstitial FSP1 is numerically highest in COLL but is only rarely found in tubules or podocytes in any other forms of FSGS.


CONCLUSIONS
We conclude that increased FSP1 may be a marker of the aggressive course of collapsing FSGS. Furthermore, DG staining is a useful adjunct to assist in distinction of FSGS versus MCD in biopsies without defining lesions.
Giannico
Giovanna
G
C-3310 MCN, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232-2561, USA. agnes.fogo@vanderbilt.edu
Yang
Haichun
H
Neilson
Eric G
EG
Fogo
Agnes B
AB
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D049030:Dystroglycans / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology*; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology; D013194:Staining and Labeling; D025721:WT1 Proteins / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D025721:WT1 Proteins; D049030:Dystroglycans