title: Impact of Ki-67 and E-cadherin expression on lymphovascular invasion in upper urinary tract urothelial carcinoma.
abstract: BACGROUND/AIM: Upper urinary tract urothelial carcinoma (UUT-UC) constitutes 5% of malignant neoplasms arising from transitional epithelium, but is more invasive than bladder cancer. Lzmphovascular invasion (LVI) is associated with biologically aggressive carcinoma and with occult metastases. The aim of this study was to investigate the correlation between LVI and immunohistochemical expression of two frequently routinely applied immunohistochemical biomarkers, Ki-67 and E-cadherin, in UUT-UC.
  
  
  METHODS
  The specimens from 106 patients with UUT-UC who had undergone nephroureterectomy were analyzed for pathologic parameters and LVI, while Ki-67 and E-cadherin expression were assessed by immunohistochemistry.
  
  
  RESULTS
  Ki-67 was overexpressed in 38% of the cases, while 45% of tumors demonstrated aberrant E-cadherin staining. The presence of LVI was significantly associated with tumor stage, grade, non-papillary growth, nodular invasion pattern, high Ki-67 labeling index and altered E-cadherin expression. Analyzing logistic regression models, we have shown that tumor properties such as stage, grade, growth and invasion pattern (p < 0.001), as well as the expression of Ki-67 and E-cadherin (p < 0.001) significantly predicted the presence of LVI. In the first model, only solid tumor architecture (p < 0.05) and nodular invasion pattern (p < 0.05) were significant predictors of LVI. In the second model, Ki-67 expression was found to improve the prediction of LVI (p < 0.05).
  
  
  CONCLUSIONS
  Our results suggest that Ki-67 overexpression is an independent predictor of LVI in UUT-UC, indicating the progression of the disease. E-cadherin staining adds no valuable information to LVI probability assessment. This emphasizes the importance of Ki-67 staining of UUT-UC sections in routine pathological practice. Patients with Ki-67 overexpression, especially in solid tumors with nodular invasion, should be monitored more closely after surgery.
authors.forename: Slavica
authors.initials: S
authors.lastname: Stojnev
authors.forename: Miljan
authors.initials: M
authors.lastname: Krstić
authors.forename: Ljubinka Janković
authors.initials: LJ
authors.lastname: Velicković
authors.forename: Ana Ristić
authors.initials: AR
authors.lastname: Petrović
authors.forename: Maja
authors.initials: M
authors.lastname: Milojković
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanović
authors.forename: Dragana
authors.initials: D
authors.lastname: Stokanović
authors.forename: Sladjana
authors.initials: S
authors.lastname: Ugrenović
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015820:Cadherins; D019394:Ki-67 Antigen