title: Clinical significance of p21-activated kinase 1 expression level in patients with upper urinary tract urothelial carcinoma.
abstract: OBJECTIVE
  The p21-activated kinase serine/threonine kinases have been outlined as the main cytoskeletal remolding regulators. The same holds true for cell proliferation and motility. They additionally have a part in cellular invasion and carcinogenesis, but the effect of p21-activated kinase 1 expression on the progression of upper urinary tract urothelial carcinoma remains unclear. Therefore, we assessed the relation of p21-activated kinase 1 positivity level to clinicopathological features in patients with upper urinary tract urothelial carcinoma.
  
  
  METHODS
  Immunohistochemical staining was performed using formalin-fixed and paraffin-embedded specimens, which were all from 124 patients with upper urinary tract urothelial carcinoma. The determination of staining level was based on the intensity of the staining along with portion of cells stained. Correlation of p21-activated kinase 1 positivity with clinicopathological parameters, including disease-specific or extravesical-recurrence-free survival, was evaluated.
  
  
  RESULTS
  Statistically significant association was observed between moderate or more than moderate p21-activated kinase 1 positivity and higher tumor grade, pathological T stage, lymphovascular invasion, history of adjuvant chemotherapy and extravesical recurrence. Positivity for p21-activated kinase 1 had a significant association with shortened disease-specific survival in a multivariate analysis among clinicopathological parameters. Strongly positive p21-activated kinase 1 expression was also one of the independent factors for shortened extravesical-recurrence-free survival time in N0M0 upper urinary tract urothelial carcinoma patients in another multivariate analysis as well as histology and lymphovascular invasion (P = 0.0304, hazard ratio = 4.425).
  
  
  CONCLUSIONS
  We conclude that our findings can help us continue a careful follow-up for upper urinary tract urothelial carcinoma patients with high p21-activated kinase 1 expression in surgical specimens.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan kksmy@sa2.so-net.ne.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Asakuma
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Horiguchi
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Isono
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Tsujita
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Seguchi
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology; D011379:Prognosis; D014551:Urinary Tract / Q000473:pathology*; D014571:Urologic Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000473:pathology*; D054462:p21-Activated Kinases / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D054462:p21-Activated Kinases
keywords: PAK1; extravesical recurrence; upper urinary tract; urothelial carcinoma