1. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses
- Author
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Eun Young Kang, Dane Cheasley, Cecile LePage, Matthew J. Wakefield, Michelle da Cunha Torres, Simone Rowley, Carolina Salazar, Zhongyue Xing, Prue Allan, David D.L. Bowtell, Anne-Marie Mes-Masson, Diane M. Provencher, Kurosh Rahimi, Linda E. Kelemen, Peter A. Fasching, Jennifer A. Doherty, Marc T. Goodman, Ellen L. Goode, Suha Deen, Paul D.P. Pharoah, James D. Brenton, Weiva Sieh, Constantina Mateoiu, Karin Sundfeldt, Linda S. Cook, Nhu D. Le, Michael S. Anglesio, C. Blake Gilks, David G. Huntsman, Catherine J. Kennedy, Nadia Traficante, D. Bowtell, G. Chenevix-Trench, A. Green, P. Webb, A. DeFazio, D. Gertig, N. Traficante, S. Fereday, S. Moore, J. Hung, K. Harrap, T. Sadkowsky, N. Pandeya, M. Malt, A. Mellon, R. Robertson, T. Vanden Bergh, M. Jones, P. Mackenzie, J. Maidens, K. Nattress, Y.E. Chiew, A. Stenlake, H. Sullivan, B. Alexander, P. Ashover, S. Brown, T. Corrish, L. Green, L. Jackman, K. Ferguson, K. Martin, A. Martyn, B. Ranieri, J. White, V. Jayde, P. Mamers, L. Bowes, L. Galletta, D. Giles, J. Hendley, K. Alsop, T. Schmidt, H. Shirley, C. Ball, C. Young, S. Viduka, Hoa Tran, Sanela Bilic, Lydia Glavinas, Julia Brooks, R. Stuart-Harris, F. Kirsten, J. Rutovitz, P. Clingan, A. Glasgow, A. Proietto, S. Braye, G. Otton, J. Shannon, T. Bonaventura, J. Stewart, S. Begbie, M. Friedlander, D. Bell, S. Baron-Hay, A. Ferrier, G. Gard, D. Nevell, N. Pavlakis, S. Valmadre, B. Young, C. Camaris, R. Crouch, L. Edwards, N. Hacker, D. Marsden, G. Robertson, P. Beale, J. Beith, J. Carter, C. Dalrymple, R. Houghton, P. Russell, M. Links, J. Grygiel, J. Hill, A. Brand, K. Byth, R. Jaworski, P. Harnett, R. Sharma, G. Wain, B. Ward, D. Papadimos, A. Crandon, M. Cummings, K. Horwood, A. Obermair, L. Perrin, D. Wyld, J. Nicklin, M. Davy, M.K. Oehler, C. Hall, T. Dodd, T. Healy, K. Pittman, D. Henderson, J. Miller, J. Pierdes, P. Blomfield, D. Challis, R. McIntosh, A. Parker, B. Brown, R. Rome, D. Allen, P. Grant, S. Hyde, R. Laurie, M. Robbie, D. Healy, T. Jobling, T. Manolitsas, J. McNealage, P. Rogers, B. Susil, E. Sumithran, I. Simpson, K. Phillips, D. Rischin, S. Fox, D. Johnson, S. Lade, M. Loughrey, N. O'Callaghan, W. Murray, P. Waring, V. Billson, J. Pyman, D. Neesham, M. Quinn, C. Underhill, R. Bell, L.F. Ng, R. Blum, V. Ganju, I. Hammond, Y. Leung, A. McCartney, M. Buck, I. Haviv, D. Purdie, D. Whiteman, N. Zeps, Anna DeFazio, Scott Kaufmann, Michael Churchman, Charlie Gourley, Andrew N. Stephens, Nicola S. Meagher, Susan J. Ramus, Yoland C. Antill, Ian Campbell, Clare L. Scott, Martin Köbel, Kylie L. Gorringe, Georgina L. Ryland, Prue E. Allan, Kathryn Alsop, Sumitra Ananda, George Au-Yeung, Maret Böhm, Alison Brand, Georgia Chenevix-Trench, Michael Christie, Yoke-Eng Chiew, Rhiannon Dudley, Nicole Fairweather, Sian Fereday, Stephen B. Fox, Neville F. Hacker, Alison M. Hadley, Joy Hendley, Gwo-Yaw Ho, Sally M. Hunter, Tom W. Jobling, Kimberly R. Kalli, Scott H. Kaufmann, Cecile Le Page, Orla M. McNally, Jessica N. McAlpine, Linda Mileshkin, Jan Pyman, Goli Samimi, Ragwha Sharma, and Ian G. Campbell
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Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,endocrine system diseases ,Concordance ,DNA Mutational Analysis ,Tp53 mutation ,Risk Assessment ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,Ovarian tumor ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,medicine ,Risk of mortality ,Humans ,neoplasms ,Observer Variation ,Ovarian Neoplasms ,Tissue microarray ,business.industry ,Australia ,Reproducibility of Results ,Middle Aged ,Prognosis ,Immunohistochemistry ,United Kingdom ,030104 developmental biology ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,Mutation ,North America ,Cohort ,Ovarian carcinomas ,Female ,Tumor Suppressor Protein p53 ,Neoplasms, Cystic, Mucinous, and Serous ,business - Abstract
TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
- Published
- 2021