p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
Por:
Kobel, M, Kang, EY, Weir, A, Rambau, PF, Lee, CH, Nelson, GS, Ghatage, P, Meagher, NS, Riggan, MJ, Alsop, J, Anglesio, MS, Beckmann, MW, Bisinotto, C, Boisen, M, Boros, J, Brand, AH, Brooks-Wilson, A, Carney, ME, Coulson, P, Courtney-Brooks, M, Cushing-Haugen, KL, Cybulski, C, Deen, S, El-Bahrawy, MA, Elishaev, E, Erber, R, Fereday, S, Fischer, A, Gayther, SA, Barquin-Garcia, A, Gentry-Maharaj, A, Gilks, CB, Gronwald, H, Grube, M, Harnett, PR, Harris, HR, Hartkopf, AD, Hartmann, A, Hein, A, Hendley, J, Hernandez, BY, Huang, YJ, Jakubowska, A, Jimenez-Linan, M, Jones, ME, Kennedy, CJ, Kluz, T, Koziak, JM, Lesnock, J, Lester, J, Lubinski, J, Longacre, TA, Lycke, M, Mateoiu, C, McCauley, BM, McGuire, V, Ney, B, Olawaiye, A, Orsulic, S, Osorio, A, Paz-Ares, L, Cajal, TRY, Rothstein, JH, Ruebner, M, Schoemaker, MJ, Shah, MT, Sharma, R, Sherman, ME, Shvetsov, YB, Singh, N, Steed, H, Storr, SJ, Talhouk, A, Traficante, N, Wang, C, Whittemore, AS, Widschwendter, M, Wilkens, LR, Winham, SJ, Benitez, J, Berchuck, A, Bowtell, DD, dos Reis, FJC, Campbell, I, Cook, LS, DeFazio, A, Doherty, JA, Fasching, PA, Fortner, RT, Garcia, MJ, Goodman, MT, Goode, EL, Gronwald, J, Huntsman, DG, Karlan, BY, Kelemen, LE, Kommoss, S, Le, ND, Martin, SG, Menon, U, Modugno, F, Pharoah, PDP, Schildkraut, JM, Sieh, W, Staebler, A, Sundfeldt, K, Swerdlow, AJ, Ramus, SJ, Brenton, JD
Publicada:
1 may 2023
Ahead of Print:
1 mar 2023
Resumen:
Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Filiaciones:
Kobel, M:
Univ Calgary, Foothills Med Ctr, Dept Pathol, Lab Med, Calgary, AB, Canada
Kang, EY:
Univ Calgary, Foothills Med Ctr, Dept Pathol, Lab Med, Calgary, AB, Canada
Weir, A:
Univ NSW Sydney, Sch Clin Med, UNSW Med & Hlth, Sydney, NSW, Australia
Univ NSW Sydney, Lowy Canc Res Ctr, Adult Canc Program, Sydney, NSW, Australia
Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia
Rambau, PF:
Univ Calgary, Foothills Med Ctr, Dept Pathol, Lab Med, Calgary, AB, Canada
Catholic Univ Hlth & Allied Sci Bugando, Pathol Dept, Mwanza, Tanzania
Lee, CH:
Univ Alberta, Dept Pathol, Lab Med, Edmonton, AB, Canada
Nelson, GS:
Univ Calgary, Cumming Sch Med, Dept Oncol, Div Gynecol Oncol, Calgary, AB, Canada
Ghatage, P:
Univ Calgary, Cumming Sch Med, Dept Oncol, Div Gynecol Oncol, Calgary, AB, Canada
Meagher, NS:
Univ NSW Sydney, Sch Clin Med, UNSW Med & Hlth, Sydney, NSW, Australia
Univ Sydney, Daffodil Ctr, Joint Venture Canc Council NSW, Sydney, NSW, Australia
Riggan, MJ:
Duke Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Med Ctr, Durham, NC USA
Alsop, J:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Anglesio, MS:
Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada
Univ British Columbia, British Columbias Gynecol Canc Res Team OVCARE, BC Canc, Vancouver, BC, Canada
Vancouver Gen Hosp, Vancouver, BC, Canada
Beckmann, MW:
Friedrich Alexander Univ Erlangen Nuremberg, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Erlangen, Germany
Bisinotto, C:
Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, Brazil
Boisen, M:
Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Sch Med, Pittsburgh, PA USA
Boros, J:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Univ Sydney, Discipline Obstet & Gynaecol, Sydney, NSW, Australia
Brand, AH:
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Univ Sydney, Discipline Obstet & Gynaecol, Sydney, NSW, Australia
Brooks-Wilson, A:
BC Canc, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada
Carney, ME:
Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI USA
Coulson, P:
Inst Canc Res, Div Genet & Epidemiol, London, England
Courtney-Brooks, M:
Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Sch Med, Pittsburgh, PA USA
Cushing-Haugen, KL:
Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA USA
Cybulski, C:
Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland
Deen, S:
Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Dept Histopathol, Nottingham, England
El-Bahrawy, MA:
Imperial Coll London, Hammersmith Hosp, Dept Metab Digest & Reprod, London, England
Elishaev, E:
Univ Pittsburgh, Dept Pathol, Sch Med, Pittsburgh, PA USA
Erber, R:
Friedrich Alexander Univ Erlangen Nuremberg, Inst Pathol, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany
Fereday, S:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Fischer, A:
Tuebingen Univ Hosp, Inst Pathol & Neuropathol, Tubingen, Germany
Gayther, SA:
Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA USA
Cedars Sinai Med Ctr, Cedars Sinai Genom Core, Los Angeles, CA USA
Barquin-Garcia, A:
Univ Hosp, HM Sanchinarro Ctr Integral Oncol Clara Campal, Madrid, Spain
Gentry-Maharaj, A:
UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England
Gilks, CB:
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
Gronwald, H:
Pomeranian Med Univ, Dept Propaedeut Phys Diagnost & Dent Physiotherap, Szczecin, Poland
Grube, M:
Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Harnett, PR:
Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia
Harris, HR:
Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA USA
Univ Washington, Dept Epidemiol, Seattle, WA USA
Hartkopf, AD:
Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Univ Hosp Ulm, Dept Gynecol & Obstet, Ulm, Germany
Hartmann, A:
Friedrich Alexander Univ Erlangen Nuremberg, Inst Pathol, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany
Hein, A:
Friedrich Alexander Univ Erlangen Nuremberg, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Erlangen, Germany
Hendley, J:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Hernandez, BY:
Univ Hawaii Canc Ctr, Canc Epidemiol Program, Honolulu, HI USA
Huang, YJ:
Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
Jakubowska, A:
Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland
Pomeranian Med Univ, Independent Lab Mol Biol & Genet Diagnost, Szczecin, Poland
Jimenez-Linan, M:
Addenbrookes Hosp, Dept Histopathol, Cambridge, England
Jones, ME:
Inst Canc Res, Div Genet & Epidemiol, London, England
Kennedy, CJ:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Univ Sydney, Discipline Obstet & Gynaecol, Sydney, NSW, Australia
Kluz, T:
Rzeszow Univ, Inst Med Sci, Dept Gynecol & Obstet, Med Coll, Rzeszow, Poland
Koziak, JM:
Alberta Hlth Serv Canc Care, Calgary, AB, Canada
Lesnock, J:
Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Sch Med, Pittsburgh, PA USA
Lester, J:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA
Lubinski, J:
Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland
Longacre, TA:
Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA
Lycke, M:
Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden
Mateoiu, C:
Univ Gothenburg, Dept Pathol, Gothenburg, Sweden
McCauley, BM:
Mayo Clin, Div Epidemiol, Dept Quantitat Hlth Sci, Rochester, MN USA
McGuire, V:
Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA USA
Ney, B:
Tuebingen Univ Hosp, Inst Pathol & Neuropathol, Tubingen, Germany
Orsulic, S:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA
Osorio, A:
Fdn Jimenez Diaz, Genet Serv, Madrid, Spain
Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Paz-Ares, L:
Spanish Natl Canc Res Ctr CNIO, H12O CNIO Lung Canc Clin Res Unit, Madrid, Spain
Hosp Univ 12 Octubre, Oncol Dept, Madrid, Spain
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain
Rothstein, JH:
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA
Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY USA
Ruebner, M:
Friedrich Alexander Univ Erlangen Nuremberg, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Erlangen, Germany
Schoemaker, MJ:
Inst Canc Res, Div Genet & Epidemiol, London, England
Shah, MT:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Sharma, R:
Westmead Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia
Sherman, ME:
Mayo Clin, Dept Hlth Sci Res, Jacksonville, FL USA
Shvetsov, YB:
Univ Hawaii Canc Ctr, Canc Epidemiol Program, Honolulu, HI USA
Singh, N:
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
Steed, H:
Univ Alberta, Dept Obstet & Gynecol, Div Gynecol Oncol, Edmonton, AB, Canada
Alberta Hlth Serv, Sect Gynecol Oncol Surg, North Zone, Edmonton, AB, Canada
Storr, SJ:
Univ Nottingham, Biodiscovery Inst, Nottingham Breast Canc Res Ctr, Nottingham, England
Talhouk, A:
Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada
Univ British Columbia, British Columbias Gynecol Canc Res Team OVCARE, BC Canc, Vancouver, BC, Canada
Vancouver Gen Hosp, Vancouver, BC, Canada
Traficante, N:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Wang, C:
Mayo Clin, Dept Quantitat Hlth Sci, Div Computat Biol, Rochester, MN USA
Whittemore, AS:
Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA USA
Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA USA
Widschwendter, M:
Univ Innsbruck, EUTOPS Inst, Innsbruck, Austria
Wilkens, LR:
Univ Hawaii Canc Ctr, Canc Epidemiol Program, Honolulu, HI USA
Winham, SJ:
Mayo Clin, Dept Quantitat Hlth Sci, Div Computat Biol, Rochester, MN USA
Benitez, J:
Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain
Berchuck, A:
Duke Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Med Ctr, Durham, NC USA
Bowtell, DD:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
dos Reis, FJC:
Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, Brazil
Campbell, I:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Cook, LS:
Univ Colorado, Sch Publ Hlth, Epidemiol, Aurora, CO USA
Univ Calgary, Community Hlth Sci, Calgary, AB, Canada
DeFazio, A:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Doherty, JA:
Univ Utah, Huntsman Canc Inst, Dept Populat Hlth Sci, Salt Lake City, UT USA
Fasching, PA:
Friedrich Alexander Univ Erlangen Nuremberg, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Erlangen, Germany
Fortner, RT:
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Canc Registry Norway, Dept Res, Oslo, Norway
Garcia, MJ:
Spanish Natl Canc Res Ctr CNIO, Struct Biol Programme, Computat Oncol Grp, Madrid, Spain
Goodman, MT:
Cedars Sinai Med Ctr, Canc Prevent & Control Program, Cedars Sinai Canc, Los Angeles, CA USA
Goode, EL:
Mayo Clin, Div Epidemiol, Dept Quantitat Hlth Sci, Rochester, MN USA
Gronwald, J:
Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland
Huntsman, DG:
Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada
Kelemen, LE:
BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada
South Carolina Dept Hlth & Environm Control, Div Acute Dis Epidemiol, Columbia, SC USA
Kommoss, S:
Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Le, ND:
BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada
Martin, SG:
Univ Nottingham, Biodiscovery Inst, Nottingham Breast Canc Res Ctr, Nottingham, England
Menon, U:
UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England
Modugno, F:
Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Sch Med, Pittsburgh, PA USA
Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA USA
Magee Womens Res Inst, Womens Canc Res Ctr, Pittsburgh, PA USA
Hillman Canc Ctr, Pittsburgh, PA USA
Pharoah, PDP:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England
Cedars Sinai Med Ctr, Dept Computat Biomed, West Hollywood, CA USA
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England
Schildkraut, JM:
Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA
Sieh, W:
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA
Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY USA
Staebler, A:
Tuebingen Univ Hosp, Inst Pathol & Neuropathol, Tubingen, Germany
Sundfeldt, K:
Univ Gothenburg, Inst Clin Sci, Sahlgrenska Ctr Canc Res, Dept Obstet & Gynecol, Gothenburg, Sweden
Swerdlow, AJ:
Inst Canc Res, Div Genet & Epidemiol, London, England
Inst Canc Res, Div Breast Canc Res, London, England
Ramus, SJ:
Univ NSW Sydney, Sch Clin Med, UNSW Med & Hlth, Sydney, NSW, Australia
Univ NSW Sydney, Lowy Canc Res Ctr, Adult Canc Program, Sydney, NSW, Australia
Brenton, JD:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
Green Submitted, Green Published, gold
|