title: Variant isoforms of CD44 expression in upper tract urothelial cancer as a predictive marker for recurrence and mortality.
abstract: The variant isoforms of CD44 (CD44v), which has been associated with treatment resistance and tumor recurrence, are contributed to the feature of some of the new cell surface markers for cancer stem cells. The aim of this study is to address the prognostic significant of CD44v expression in upper tract urothelial cancer (UTUC).
  
  
  
  We retrospectively analyzed the medical records of 110 patients treated surgically for≥pT2 UTUC. To determine the biological significance of CD44v in UTUC, we examined the immunohistochemical expression of CD44v9 and its association with clinical features and oncological outcomes.
  
  
  
  During the mean follow-up of 4.8 years, tumor recurrence, including local and distant metastasis, was observed in 57 patients (51.8%), and 42 patients (38.2%) died of the disease. The incidence of ureter cancers was significantly higher in patients expressing CD44v9. In this series, 37 patients in the CD44v9-positive group (45.1%) and 5 (17.9%) in the CD44v9-negative group died of the disease. Kaplan-Meier curves revealed that cancer-specific survival and recurrence-free survival rates were significantly lower in the CD44v9-positive group than in the CD44v9-negative group (P = 0.032 and P = 0.038, respectively). A multivariate analysis identified the expression of CD44v9 as one of the independent risk factors for cancer-specific survival (P = 0.040, hazard ratio = 2.67) in addition to tumor grade G3, and also for recurrence-free survival (P = 0.028, hazard ratio = 2.33), in addition to tumor grade G3 and lymphovascular invasion.
  
  
  
  The expression of CD44v9 may be a new biomarker of malignant potential in muscle invasive UTUC and provide additional prognostic information in patients with UTUC.
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hagiwara
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan. Electronic address: eiji-k@kb3.so-net.ne.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kikuchi
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009392:Nephrectomy; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism; D012189:Retrospective Studies; D014516:Ureteral Neoplasms / Q000175:diagnosis / Q000473:pathology; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D020033:Protein Isoforms
keywords: CD44; Nephroureterectomy; Recurrence; Survival; Upper tract urothelial cancer