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Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas

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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.

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Acknowledgments

We would like to thank Kathleen Cieply and Carol Sherer in the FISH and aCGH Laboratory and Kimberly Fuhrer in the Developmental Laboratory of the Department of Pathology University of Pittsburgh Medical Center for their excellent technical assistance.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology—PUH A610, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA, 15213, USA

    Sanja Dacic

  2. Institute of Pathology, Graz, Austria

    Hannelore Kothmaier, Iris Halbwedl & Helmut Popper

  3. University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Stephanie Land & Yongli Shuai

  4. Instituto di Anatomia Pathologica, Pavia, Italy

    Patrizia Morbini

  5. Ospedale Umberto, Mestre, Venice, Italy

    Bruno Murer

  6. Department of Human Pathology and Oncology, University of Florence, Florence, Italy

    Camilla Comin

  7. CHU Cote de Nacre, Caen, France

    Françoise Galateau-Salle

  8. Ataturk Chest Disease Hospital, Ankara, Turkey

    Funda Demirag

  9. Adana University, Adana, Turkey

    Handan Zeren

  10. Cardiff and Vale NHS Trust Llandough Hospital, Cardiff, UK

    Richard Attanoos & Alan Gibbs

  11. The Methodist Hospital, Houston, TX, USA

    Philip Cagle

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  1. Sanja Dacic
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  2. Hannelore Kothmaier
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  15. Helmut Popper
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Correspondence to Sanja Dacic.

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Dacic, S., Kothmaier, H., Land, S. et al. Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas. Virchows Arch 453, 627–635 (2008). https://doi.org/10.1007/s00428-008-0689-3

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  • DOI: https://doi.org/10.1007/s00428-008-0689-3

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