Wang Yu, Roma Andres, Nolley Rosalie, Abdul-Karim Fadi, Peehl Donna M, Eng Charis
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.
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
Endocr Relat Cancer. 2014 Aug;21(4):579-86. doi: 10.1530/ERC-14-0148.
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.
患有器官局限性前列腺癌（CaP）的男性通常接受根治性前列腺切除术。尽管术后特征相似，但很大一部分具有中等进展风险的男性会经历前列腺特异性抗原（PSA）定义的失败，而其他男性则有无复发生存期（RFS）。需要额外的预后标志物来预测这些患者的预后。KLLN是一种调节细胞周期并诱导癌细胞凋亡的转录因子。我们已经表明KLLN是一种雄激素调节基因，原发性CaP中KLLN表达的缺失与高Gleason评分相关。在这项回顾性研究中，我们评估了109例具有中等风险CaP的男性高级别恶性肿瘤成分中的KLLN表达。与核KLLN阳性患者相比，核KLLN阴性肿瘤患者术前血清PSA水平显著更高（12.24±2.37 ng/ml），肿瘤体积更大（4.61±0.71 cm³）（分别为8.35±2.45 ng/ml，P = 0.03，和2.66±0.51 cm³，P < 0.0001）。核KLLN阳性肿瘤均无包膜侵犯，而34%的核KLLN阴性肿瘤有包膜侵犯（P = 0.004）。肿瘤细胞核中维持KLLN表达，但细胞质或基质中不维持，与术后改善的RFS相关（P = 0.002）。核KLLN阳性肿瘤患者中只有7%出现肿瘤复发，而KLLN阴性组中60%的患者发生PSA定义的失败，中位复发时间为6.6个月（P = 0.0003）。我们的数据表明，KLLN表达可作为一种预后标志物来预测中等风险患者的预后，这可为术后管理提供有用信息。
