title: Retrospective Evaluation of Risk Factors and Immunohistochemical Findings for Pre-Neoplastic and Neoplastic lesions of Upper Urinary Tract in Patients with Chronic Nephrolithiasis.
abstract: BACKGROUND
  Urinary stones are known predisposing factors for upper urinary tract carcinoma (UUTC) which are commonly detected at advanced stage with poor outcome because of rarity and lack of specific criteria for early detection.
  
  
  OBJECTIVE
  The main aim was to evaluate the impact of age, gender andstone characteristics on risk of developing UUTC in patients with chronic nephrolithiasis. We also discuss the role of aberrant angiogenesis (AA) and immunohistochemical expression of p53, p16INK4a, CK20 and Ki-67 in diagnosis of pelvicalyceal neoplastic (NL) and pre-neoplastic lesions (PNL) in these patients.
  
  
  METHODS
  Retrospective analysis of pelvicalyceal urothelial lesions from 88 nephrectomy specimens were carried out in a tertiary care centre from June 2012 to December 2014. Immunohistochemistry (IHC) was performed on 37 selected cases. Computed image analysis was performed to analyse aberrant angiogenesis.
  
  
  RESULTS
  All UUTC (5.7%) and metaplastic lesions were found to be associated with stones. Some 60% were pure squamous cell carcinoma and 40% were transitional cell carcinoma. Odd ratios for developing NL and PNL lesions in presence of renal stone, impacted stones, multiple and large stag horn stones were 9.39 (95% CI 1.15-76.39, p value 0.05), 6.28 (95% CI 1.59-24.85, p value 0.000) and 7.4 (95% CI, 2.29-23.94, p value 0.001) respectively. When patient age was ≥ 55, the odds ratio for developing NL was 3.43 (95% CI 1.19-9.88, p value 0.019). IHC analysis showed that mean Ki-67 indices were 3.15 ± 3.63 % for non-neoplastic lesions, 10.0±9.45 % for PNL and 28.0± 18.4% for NL. Sensitivity and specificity of CK20, p53, p16INK4a, AA were 76% and 95.9%; 100% and 27.5%; 100% and 26.5%; 92.3 % and 78.8% respectively.
  
  
  CONCLUSIONS
  Age ≥55 years, large stag horn stones, multiple stones and impacted stones are found to be associated with increased risk of NL and PNL in UUT. For flat lesions, a panel of markers, Ki 67 index >10 and presence of aberrant angiogenesis were more useful than individual markers.
authors.affiliation: Department of Biotechnology, Manipur University, Imphal, India E-mail : shanjulisam@gmail.com.
authors.forename: Fanny Sharadkumar
authors.initials: FS
authors.lastname: Desai
authors.forename: Jitendra
authors.initials: J
authors.lastname: Nongthombam
authors.forename: Lisam Shanjukumar
authors.initials: LS
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D053040:Nephrolithiasis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014571:Urologic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor