title: Correlation of mitotic indices, AgNor count, Ki-67 and Bcl-2 with grade and stage in papillary urothelial bladder cancer.
abstract: OBJECTIVE
  To evaluate the mutual inter-relationship of mitotic indices, argyrophilic nuclear organizer regions (AgNOR) count, Ki-67 and B-cell lymphoma 2 protein (bcl-2) in papillary urothelial bladder cancer (pUBC), and their correlation with grade and stage. To establish the cut-off values of these markers to detect high grade and muscle invasive bladder cancer.
  
  
  METHODS
  Fifty-four patients with primary pUBC who underwent transurethral resection / radical cystectomy were analyzed retrospectively. Cell proliferation was assessed by Ki-67 labelling index, mean AgNOR count, mitotic count, mitotic activity index and mitosis/ volume index. Immunohistochemistry was done to see bcl-2 and Ki-67 expression. Correlation of these indices with tumor grade and stage and amongst themselves was assessed. The receiver operating characteristic (ROC) curves were drawn to establish the cut-off values.
  
  
  RESULTS
  We found a strong positive correlation of mitotic indices and Ki-67 with tumor grade (P = .000), stage (P < .05) and bcl-2 (P = .000). AgNOR count correlated positively with the grade (P = .006), mitotic indices and Ki-67 (P = .032) but not with tumor stage and bcl-2. Cytoplasmic bcl-2 immunopositivity was seen in 42.3% of low grade pUBC and 85.7% of high grade pUBC cases (P = .001). bcl-2 positivity was seen in 85% of muscle invasive pUBC as compared to only 52.9% of superficial cases. Ki-67 ≥ 32.5%, ≥ 14 mitoses/10 high power fields (hpf), ≥ 11.20 mitoses/mm2, ≥ 0.75 mitoses/100 tumor cells and AgNOR ≥ 11.55 are 100% specific for high grade bladder carcinoma. Ki-67 ≥ 59% and mitoses ≥ 36.50 per 10 hpf can indicate muscle invasion with 100% specificity.
  
  
  CONCLUSIONS
  Cut-off values for Ki-67, mitotic indices and AgNOR can confirm high grade bladder carcinoma in equivocal cases. Ki-67 and mitotic count can serve as potential and reliable indicators of muscle invasion.
authors.affiliation: Department of Pathology, University College of Medical Sciences and Guru Teg BahadurHospital,Delhi,India.dr.surbhi4you@gmail.com.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Department of Pathology, University College of Medical Sciences and Guru Teg BahadurHospital,Delhi,India.
authors.forename: Usha Rani
authors.initials: UR
authors.lastname: Singh
authors.affiliation: Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital,Delhi,India.
authors.forename: Sonal
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Kaur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C051963:nucleolar organizer region associated proteins