title: MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Health Sciences, Lahore, Punjab, Pakistan.
authors.forename: Muhammad Zain
authors.initials: MZ
authors.lastname: Mehdi
authors.affiliation: Department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore, Punjab, Pakistan.
authors.forename: Abdul Hanan
authors.initials: AH
authors.lastname: Nagi
authors.affiliation: Department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore, Punjab, Pakistan.
authors.forename: Nadia
authors.initials: N
authors.lastname: Naseem
mesh_terms: D002292:Carcinoma, Renal Cell / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2 / Q000737:chemistry*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015588:Observer Variation; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry*
chemical_list: D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D064111:Minichromosome Maintenance Complex Component 2
keywords: Carcinoma, Renal Cell; Cell Proliferation; Ki-67 Antigen