title: Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas.
abstract: Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.
authors.affiliation: Department of Pathology-PUH A610, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213, USA. dacics@upmc.edu
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.forename: Hannelore
authors.initials: H
authors.lastname: Kothmaier
authors.forename: Stephanie
authors.initials: S
authors.lastname: Land
authors.forename: Yongli
authors.initials: Y
authors.lastname: Shuai
authors.forename: Iris
authors.initials: I
authors.lastname: Halbwedl
authors.forename: Patrizia
authors.initials: P
authors.lastname: Morbini
authors.forename: Bruno
authors.initials: B
authors.lastname: Murer
authors.forename: Camilla
authors.initials: C
authors.lastname: Comin
authors.forename: Françoise
authors.initials: F
authors.lastname: Galateau-Salle
authors.forename: Funda
authors.initials: F
authors.lastname: Demirag
authors.forename: Handan
authors.initials: H
authors.lastname: Zeren
authors.forename: Richard
authors.initials: R
authors.lastname: Attanoos
authors.forename: Alan
authors.initials: A
authors.lastname: Gibbs
authors.forename: Philip
authors.initials: P
authors.lastname: Cagle
authors.forename: Helmut
authors.initials: H
authors.lastname: Popper
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16