title: Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence.
  
  
  METHODS
  The expression of cyclin-dependent kinase inhibitor p16/INK4A was evaluated by immunohistochemistry using tumour biopsy specimens from 88 MPM cases and a semi-quantitative score for p16/INK4A expression was obtained. Post-diagnosis survival and the survival benefit of chemotherapeutic intervention was correlated with p16/INK4A expression.
  
  
  RESULTS
  A low, intermediate and high score for p16/INK4A expression was observed for 45 (51.1%), 28 (31.8%) and 15 (17.1%) of the MPM cases, respectively. Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression (log-rank P<0.001). Those patients with sustained p16/INK4A expression who received chemotherapy also had a better survival than those treated patients whose tumours had lost p16/INK4A expression (log-rank P<0.001).
  
  
  CONCLUSIONS
  Sustained p16/INK4A expression predicts better post-diagnosis survival in MPM and also better survival following chemotherapeutic intervention.
authors.affiliation: Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: C J
authors.initials: CJ
authors.lastname: Jennings
authors.affiliation: Department of Anatomy and Histopathology, Dell' Angelo Hospital, Via Paccagnella 11, Mestre, 30174 VE, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Murer
authors.affiliation: Department of Histopathology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: O'Grady
authors.affiliation: Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: L M
authors.initials: LM
authors.lastname: Hearn
authors.affiliation: Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: B J
authors.initials: BJ
authors.lastname: Harvey
authors.affiliation: Department of Histopathology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: E W
authors.initials: EW
authors.lastname: Kay
authors.affiliation: 1] Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland [2] Perdana University - Royal College of Surgeons in Ireland School of Medicine, Jalan MAEPS Perdana, 43400 Serdang, Selangor, Malaysia.
authors.forename: W
authors.initials: W
authors.lastname: Thomas
mesh_terms: D045744:Cell Line, Tumor; D015331:Cohort Studies; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins