title: Piwil 2 expression is correlated with disease-specific and progression-free survival of chemotherapy-treated bladder cancer patients.
abstract: Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated the Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan Meier analyses and univariate/multivariate Cox's regression hazard models.In a multivariate Cox's regression, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (RR=2.7; P=0.004 and RR=2.4; P=0.027). Likewise,, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR=2.3; P=0.023 and RR=2.2; P=0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P=0.005) compared to patients with strong expression. Considering only patients with high grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This implicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients.
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.affiliation: Department of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jung
authors.affiliation: Siemens Healthcare Diagnostics, Elkhart, Indiana, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pugia
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.affiliation: Department of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bertz
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Nolte
authors.affiliation: Department of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.affiliation: Urologische Gemeinschaftspraxis, Prüner Gang and Department of Urology, Städtisches Krankenhaus, Kiel, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Department of Urology, Saarland University, Homburg, Germany.
authors.forename: Carsten-H
authors.initials: CH
authors.lastname: Ohlmann
authors.affiliation: Department of Urology, Saarland University, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.affiliation: Department of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D042541:Intracellular Space / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D021381:Protein Transport; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
chemical_list: D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; C486868:PIWIL2 protein, human