title: Nuclear KLLN expression associates with improved relapse-free survival for prostate carcinoma.
abstract: Men with organ-confined prostate cancer (CaP) are often treated with radical prostatectomy. Despite similar postoperative characteristics, a significant proportion of men with an intermediate risk of progression experience prostate-specific antigen (PSA)-defined failure, while others have relapse-free survival (RFS). Additional prognostic markers are needed to predict the outcome of these patients. KLLN is a transcription factor that regulates the cell cycle and induces apoptosis in cancer cells. We have shown that KLLN is an androgen-regulated gene and that loss of KLLN expression in primary CaP is associated with high Gleason score. In this retrospective study, we evaluated KLLN expression in the high-grade malignancy components from 109 men with intermediate risk CaP. Patients with nuclear KLLN-negative tumors had significantly higher preoperative serum PSA levels (12.24±2.37 ng/ml) and larger tumor volumes (4.61±0.71 cm(3)) compared with nuclear KLLN-positive patients (8.35±2.45 ng/ml, P=0.03, and 2.66±0.51 cm(3), P<0.0001, respectively). None of the nuclear KLLN-positive tumors had capsular penetration, whereas 34% of nuclear KLLN-negative tumors (P=0.004) had capsular penetration. Maintaining KLLN expression in tumor nuclei, but not in cytoplasm or stroma, associated with improved RFS after surgery (P=0.002). Only 7% of patients with nuclear KLLN-positive tumors had tumor recurrence, while 60% of patients in the KLLN-negative group developed PSA-defined failure with median relapse time of 6.6 months (P=0.0003). Our data suggest that KLLN expression may be used as a prognostic marker to predict outcome for intermediate risk patients, which could provide useful information for postoperative management.
authors: Genomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors: Yu
authors: Y
authors: Wang
authors: Genomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors: Andres
authors: A
authors: Roma
authors: Genomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors: Rosalie
authors: R
authors: Nolley
authors: Genomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors: Fadi
authors: F
authors: Abdul-Karim
authors: Genomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors: Donna M
authors: DM
authors: Peehl
authors: Genomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USAGenomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USAGenomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USAGenomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyStanford University School of Medicine, Stanford, California 94305, USATaussig Cancer InstituteStanley Shalom Zielony Institute for Nursing ExcellenceCleveland Clinic, Cleveland, Ohio 44195, USADepartment of Genetics and Genome SciencesCASE Comprehensive Cancer CenterCase Western Reserve University School of Medicine, Cleveland, Ohio 44106, USAGenomic Medicine InstituteDepartment of Anatomic PathologyCleveland Clinic, Cleveland, Ohio 44195, USADepartment of UrologyS
authors: Charis
authors: C
authors: Eng
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012008:Recurrence; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C554482:KLLN protein, human; D025521:Tumor Suppressor Proteins
keywords: KLLN; PSA failure; prostate cancer; radical prostatectomy; relapse-free survival