Molecular Expression of Podocytes in the Variants of Focal Segmental Glomerulosclerosis
Leonardo A Testagrossa, Raymundo Azevedo Neto, Viktoria Woronik, Denise MAC Malheiros. Hospital das Clinicas da Faculdade de Medicina da USP, Sao Paulo, SP, Brazil; Faculdade de Medicina da USP, Sao Paulo, SP, Brazil
Background: Focal segmental glomerulosclerosis (FSGS) is the most prevalent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Primary FSGS is characterized clinically by affecting young people and causing severe proteinuria and nephrotic syndrome. The pathogenesis is related to podocyte injury, which may be due to several factors: viruses, drugs, immunological, etc. In 2004, the Columbia classification of FSGS identified five histological variants of the disease: collapsing (COL), usual (NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). Several studies have demonstrated molecular changes in podocytes of FSGS patients, which were observed in molecules involved in the filtering and structural function of these cells like nephrin, podocina, CD2AP, α-actinin-4, synaptopodin, etc. as well as in molecules of podocyte differentiation like CD10, WT-1, and of cell division: Ki-67 and PCNA. The objective of this study was to classify the FSGS biopsies according to the Columbia classification and to analyze the occurrence of molecular changes on these variants.
Design: 131 cases of renal biopsies with a diagnosis of primary FSGS in the period 1996 to 2006 were classified in COL, NOS, TIP, PHI and CEL, and then stained with immunohistochemical reactions to the primary antibodies: CD10, WT-1, Vimentin, Synaptopodin, α-actinin-4, GLEPP-1, cytokeratin 8-18, cytokeratin 19, and Ki-67.
Results: FSGS classification resulted in 38.2% of NOS variant, 36.6% COL, 14.5% TIP, 6.9% PHI and 3.8% CEL. The podocytes of COL variant biopsies were distinguished from the other variants for having lost the expression of CD10 (p<0,01), WT-1 (p<0,01) and α-actinin-4 (p <0,05) in podocytes. Furthermore, they gained expression of the cytokeratin 8-18 (p <0.05) and 19 (p <0.01). The group of CEL and COL variants differed from the group pf other variants regarding the expression of cell division marker Ki-67 in podocytes (p <0.05).
Conclusions: COL variant of FSGS presents molecular changes in podocytes that differs from other variants and can be demonstrated by immunohistochemistry. The differential diagnosis of this variant is important because of the worse clinical outcome in comparison with TIP, NOS, PHI and CEL variants, so the identification of these markers by immunohistochemical may be useful in the diagnosis on the routine practice and also for the better compreention of the disease.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 283, Wednesday Afternoon