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.

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

“…Here, we present the first study to examine the genomic and transcriptional differences between HIV(+) and HIV(−) GCB‐DLBCL determined using the Lymph2Cx GEP assay. IHC results showed that HIV(+) tumors are significantly more proliferative than their HIV(−) counterparts by Ki67 staining, which corroborates the GEP signature that revealed significant increases in a number of DNA replication and cell cycle genes; including MCM2 , MCM4 and MCM7 , all three of which have been reported to be alternative proliferation markers to Ki67 …”

CORRELATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND Ki-67 EXPRESSION WITH HISTOLOGICAL GRADE AND STAGE OF RENAL CELL CARCINOMA

“…We found no significant correlation between Ki-67 expression and histologic tumour subtypes. This was similar to the studies conducted by Wong PK et al 28 and Mehdi MZ et al 15 In current study, there was significant association between VEGF grades and Ki-67 labelling index of RCCs (p<0.0001). The Ki-67 labelling index showed significantly increasing trend with the increase in VEGF grades of the tumours which was concordant with Bürgesser M et al, 18 However, this finding was discordant with Matušan-Ilijaš K et al 22 who did not find any association between these markers.…”

“…Ki-67 index was expressed as percentage of positive staining cells among total number of invasive cells in the area scored. We used our own laboratory cut-off value of 15% according to Mehdi MZ et al 15 For VEGF, staining was determined semiquantitatively according to a three-grade scale according to Yildiz E et al 16 :  0: no staining of tumour cells;  1+: membranous stain with no cytoplasmic immunostaining or with light cytoplasmic staining of some tumour cells (<50%);  2+: diffuse and strong membranous and cytoplasmic staining of most tumour cells (>50%). 18.0% cases showed sarcomatoid differentiation whereas 4.0% cases showed rhabdoid differentiation.…”

“…(p<0.00001) ( Among histological parameters, WHO/ISUP nuclear grade is considered the most important prognostic parameter but it often shows substantial intra-observer and inter-observer variation. 15 There are no current immunohistochemical prognostic markers which are routinely used for RCCs. In this era of new treatment possibilities, there is need for better prognostic tools to plan the treatment and follow-up of RCC patients.…”

“…Proliferation index of RCC as determined by Ki-67 is known to have prognostic importance in univariate and multi-variate analysis and it also correlates with tumour grade. 15 In recent years importance has been given to the expression of different angiogenic factors like VEGF in RCCs. 18 On this background, we conducted a study to assess VEGF expression and Ki-67 labelling index in RCCs and document the possibility of a correlation between these markers with different known prognostic parameters of RCC by IHC.…”