title: Differential Predictive Roles of A- and B-Type Nuclear Lamins in Prostate Cancer Progression.
abstract: BACKGROUND
  Prostate cancer (PCa) is the most common cancer among men in western countries. While active surveillance is increasingly utilized, the majority of patients are currently treated with radical prostatectomy. In order to avoid over-treatment, there is an indisputable need for reliable biomarkers to identify the potentially aggressive and lethal cases. Nuclear intermediate filament proteins called lamins play a role in chromatin organization, gene expression and cell stiffness. The expression of lamin A is associated with poor outcome in colorectal cancer but to date the prognostic value of the lamins has not been tested in other solid tumors.
  
  
  METHODS
  We studied the expression of different lamins with immunohistochemistry in a tissue microarray material of 501 PCa patients undergoing radical prostatectomy and lymph node dissection. Patients were divided into two staining categories (low and high expression). The correlation of lamin expression with clinicopathological variables was tested and the association of lamin status with biochemical recurrence (BCR) and disease specific survival (DSS) was further analyzed.
  
  
  RESULTS
  Low expression of lamin A associated with lymph node positivity (p<0.01) but not with other clinicopathological variables and low expression had a borderline independent significant association with DSS (HR = 0.4; 95% CI 0.2-1.0; p = 0.052). Similarly, low lamin C expression associated with poorer survival (HR = 0.2; 95% CI 0.1-0.6; p = 0.004). Lamin B1 expression did not associate with clinicopathological variables but high expression independently predicted BCR in multivariable Cox regression analysis (HR = 1.8; 95% CI 1.1-2.9; p = 0.023). Low expression of lamin B2 correlated with lymph node positivity (p<0.01) and predicted unfavorable DSS (HR = 0.4; 95% CI 0.2-1.0; p = 0.047).
  
  
  CONCLUSIONS
  These results suggest differential roles for lamins in PCa progression. Reduced amounts of lamin A/C and B2 increase risk for lymph node metastasis and disease specific death possibly through increased nuclear deformability while high expression of lamin B1 predicts disease recurrence.
authors.affiliation: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland; MediCity, Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Irena
authors.initials: I
authors.lastname: Saarinen
authors.affiliation: Department of Pathology, Helsinki University Hospital and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mirtti
authors.affiliation: Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Seikkula
authors.affiliation: Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Boström
authors.affiliation: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland; MediCity, Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Taimen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003937:Diagnosis, Differential; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000032:analysis* / Q000378:metabolism; D034921:Lamin Type B / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D034904:Lamin Type A; D034921:Lamin Type B