The value of proliferating cell nuclear antigen (PCNA)-cyclin in the assessment of cell proliferation in glomerulonephritis

Abstract

Proliferating cell nuclear antigen (PCNA)/ cyclin is an acidic nuclear protein increasing from the late G1 to S phases of the cell cycle and whose detection parallels other standard methods for assessing cell proliferation. The aim of this study was to investigate PCNA expression in normal and diseased human kidneys, in order to clarify cell proliferation in renal tissue and to define a possible correlation of its expression with various types of glomerulonephritis (GN). The immunohistochemical avidin-biotin complex (ABC) method was used for the demonstration of PCNA applying the monoclonal antibody PC-10 to paraffin sections from: 10 normal kidneys, 55 renal biopsies with various types of proliferative GN (PGN), 44 renal biopsies with various types of non proliferative GN (NPGN). In PCNA-positive renal biopsies with GN the antigen showed a heterogeneous nuclear expression in occasional or few mesangial and glomerular epithelial cells as well as in a greater number of tubular epithelial cells. PCNA was expressed in 20% of normal kidneys and in 38% of renal biopsies with GN. The frequency of PCNA expression was significantly increased in the cases of PGN (47%) compared to that observed in the cases of NPGN (27%) (p=0.03). PCNA was detected in 10124 cases of IgA nephropathy, in 314 cases of IgM nephropathy, in 5/14 of other types of primary PGN and in 8/13 of secondary PGN. PCNA expression was not correlated with the degree of mesangial cellularity in PGN. Moreover, there was no significant difference in PCNA expression between primary and secondary PGN. PCNA demonstrated an intense expression in the majority of epithelial cells forming cellular crescents in 811 1 cases of PGN. In conclusion, PCNA was observed more frequently in diseased than in normal kidneys. The significant increase in the frequency of PCNA intraglomerular expression in PGN suggests that PCNA has a certain value in the assessment of mesangial proliferation. Moreover, the increased PCNA expression in tubular epithelial cells especially in PGN, indicates their proliferative state and may be correlated with their proposed activation and role in the progression of renal injury