MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis

ABSTRACT Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. Material and Methods: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Results: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Conclusion: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.

reparative role of CD34[+] cells in human nephropathies

Stem cells are defined by the two properties of self renewal and pleuripotency. In different adult tissues, they generate new cells either continuously or in response to injury depending on local factors in the surrounding microenvironment which direct their line of differentiation. Circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells [tubular epithelial cells, podocytes, mesangial cells and fib roast]. This study included 36 human renal biopsies of different types of glomerulonephritis to determine the role of stem cells in the repair process of glomerulonephritis. Renal biopsies were stained immunohistochemically with monoclonal anti - CD34 antibodies, the stem cell marker as well as alpha SMA, Vimentin, Proliferating Cell Nuclear Antigen [PCNA], Insitu End Labeling [ISEL], CD68. Positivity was evaluated using a point counting technique in the glomeruli and by counting individual positive cells per HPF [X400] in the interstitium. To rule out the endothelial nature of positive cells, double staining for factor IIX related antigen and CD31 was done. CD34 positive cells were detected in the glomerular mesangial areas with peripheral accentuation suggestive of a visceral epithelial distribution, tubular epithelial cells [cytoplasmic in 3/36 cases and in the luminal border of the rest of the cases] as well as in isolated cells in the renal interstitium, these cells also double stained for alpha SMA. CD34 positivity was counted in the glomeruli [3.05 +/- 0.58], tubules [6.38 +/- 2.58] and for interstitial areas [9.76 +/- 2.34]. Significant positive correlation between glomerular CD34 and glomerular regeneration ratio was found. These results imply the presence and may be a role for stem cells in the repair process of glomerulonephritis