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p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies
Abstract
TP53 mutations are considered a surrogate biomarker of the serous‐like ‘copy number high’ molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts TP53 mutations identified by next‐generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (POLE mut). A secondary aim assessed inter‐laboratory variability in p53 IHC. From a total of 207 cases from five centres (37–49 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (n = 164) and curated tagged‐amplicon NGS TP53 sequencing results (n = 177). Following consensus review, local and central p53 IHC results were concordant in 156/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild‐type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and TP53 mutation was 155/168 (92.3%) overall, and 117/123 (95.1%) after excluding MMRd and POLE mut EC. Three (3/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable TP53 mutation. Subclonal mutant p53 IHC expression was observed in 9/177 (5.1%) cases, of which four were either MMRd or POLE mut. Mutant pattern p53 IHC was observed in 63/63 (100%) serous carcinomas that were MMR‐proficient/POLE exonuclease domain wild‐type. Optimised p53 IHC performs well as a surrogate test for TP53 mutation in EC biopsies, demonstrates excellent inter‐laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Cites
Integrated genomic characterization of endometrial carcinoma
The Cancer Genome Atlas Research Network, & Levine, D. A. (2013) · Nature · doi:10.1038/nature12113 · Cited by 5,784 · cited 4×
“In the molecular classification of EC, the presence of TP53 mutation or p53abn IHC is only a surrogate for CN-high molecular subtype if the POLEmut and MMRd tumours are excluded [7,14,17].”
BackgroundInfluentialPredicting Functional Effect of Human Missense Mutations Using PolyPhen‐2
Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0720s76 · Cited by 3,705
ClinVar: public archive of relationships among sequence variation and human phenotype
Landrum, M. J., Lee, J. M., Riley, G. R., Jang, W., Rubinstein, W. S., Church, D. M., & Maglott, D. R. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1113 · Cited by 3,516
Two pathogenetic types of endometrial carcinoma
Bokhman, J. V. (1983) · Gynecologic Oncology · doi:10.1016/0090-8258(83)90111-7 · Cited by 2,494
SIFT web server: predicting effects of amino acid substitutions on proteins
Sim, N.-L., Kumar, P., Hu, J., Henikoff, S., Schneider, G., & Ng, P. C. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks539 · Cited by 2,411
T antigen is bound to a host protein in SY40-transformed cells
LANE, D. P., & CRAWFORD, L. V. (1979) · Nature · doi:10.1038/278261a0 · Cited by 2,394
COSMIC: exploring the world's knowledge of somatic mutations in human cancer
Forbes, S. A., Beare, D., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., Ding, M., Bamford, S., Cole, C., Ward, S., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1075 · Cited by 2,283
Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., & Olivier, M. (2007) · Human Mutation · doi:10.1002/humu.20495 · Cited by 1,598 · cited 1×
“Rare SNVs with potential tolerated or benign predictions were further characterised using the IARC (WHO) TP53 mutation database [27] (supplementary material, Table S2).”
MethodFinlay, C. A., Hinds, P. W., Tan, T. H., Eliyahu, D., Oren, M., & Levine, A. J. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.531 · Cited by 1,144
A clinically applicable molecular-based classification for endometrial cancers
Talhouk, A., McConechy, M. K., Leung, S., Li-Chang, H. H., Kwon, J. S., Melnyk, N., Yang, W., Senz, J., Boyd, N., Karnezis, A. N., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.190 · Cited by 971
Self-citationStelloo, E., Nout, R. A., Osse, E. M., Jürgenliemk-Schulz, I. J., Jobsen, J. J., Lutgens, L. C., van der Steen-Banasik, E. M., Nijman, H. W., Putter, H., Bosse, T., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2878 · Cited by 846
Self-citationDriver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary
Ahmed, A. A., Etemadmoghadam, D., Temple, J., Lynch, A. G., Riad, M., Sharma, R., Stewart, C., Fereday, S., Caldas, C., deFazio, A., et al. (2010) · The Journal of Pathology · doi:10.1002/path.2696 · Cited by 787
Self-citationKommoss, S., McConechy, M. K., Kommoss, F., Leung, S., Bunz, A., Magrill, J., Britton, H., Kommoss, F., Grevenkamp, F., Karnezis, A., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy058 · Cited by 776
Self-citationClinicopathological and molecular characterisation of ‘multiple‐classifier’ endometrial carcinomas
León‐Castillo, A., Gilvazquez, E., Nout, R., Smit, V. T., McAlpine, J. N., McConechy, M., Kommoss, S., Brucker, S. Y., Carlson, J. W., Epstein, E., et al. (2020) · The Journal of Pathology · doi:10.1002/path.5373 · Cited by 415
Self-citationInterpretation of somatic POLE mutations in endometrial carcinoma
León‐Castillo, A., Britton, H., McConechy, M. K., McAlpine, J. N., Nout, R., Kommoss, S., Brucker, S. Y., Carlson, J. W., Epstein, E., Rau, T. T., et al. (2020) · The Journal of Pathology · doi:10.1002/path.5372 · Cited by 409
Self-citationKöbel, M., Ronnett, B. M., Singh, N., Soslow, R. A., Gilks, C. B., & McCluggage, W. G. (2019) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0000000000000488 · Cited by 408
Self-citationOptimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma
Köbel, M., Piskorz, A. M., Lee, S., Lui, S., LePage, C., Marass, F., Rosenfeld, N., Mes Masson, A., & Brenton, J. D. (2016) · The Journal of Pathology: Clinical Research · doi:10.1002/cjp2.53 · Cited by 387
Self-citationPractical guidance for mismatch repair-deficiency testing in endometrial cancer
Stelloo, E., Jansen, A. M. L., Osse, E. M., Nout, R. A., Creutzberg, C. L., Ruano, D., Church, D. N., Morreau, H., Smit, V. T. H. B. M., van Wezel, T., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdw542 · Cited by 342
Self-citationBosse, T., Nout, R. A., McAlpine, J. N., McConechy, M. K., Britton, H., Hussein, Y. R., Gonzalez, C., Ganesan, R., Steele, J. C., Harrison, B. T., et al. (2018) · American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001020 · Cited by 341
Self-citationPrognostic Significance of POLE Proofreading Mutations in Endometrial Cancer
Church, D. N., Stelloo, E., Nout, R. A., Valtcheva, N., Depreeuw, J., ter Haar, N., Noske, A., Amant, F., Tomlinson, I. P. M., Wild, P. J., et al. (2015) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/dju402 · Cited by 332
Self-citationThe genetic landscape of endometrial clear cell carcinomas
DeLair, D. F., Burke, K. A., Selenica, P., Lim, R. S., Scott, S. N., Middha, S., Mohanty, A. S., Cheng, D. T., Berger, M. F., Soslow, R. A., et al. (2017) · The Journal of Pathology · doi:10.1002/path.4947 · Cited by 227
Talhouk, A., Hoang, L. N., McConechy, M. K., Nakonechny, Q., Leo, J., Cheng, A., Leung, S., Yang, W., Lum, A., Köbel, M., et al. (2016) · Gynecologic Oncology · doi:10.1016/j.ygyno.2016.07.090 · Cited by 225
Self-citationMcConechy, M. K., Talhouk, A., Li-Chang, H. H., Leung, S., Huntsman, D. G., Gilks, C. B., & McAlpine, J. N. (2015) · Gynecologic Oncology · doi:10.1016/j.ygyno.2015.01.541 · Cited by 218
Self-citationTP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers
Schultheis, A. M., Martelotto, L. G., Filippo, M. R. D., Piscuglio, S., Ng, C. K. Y., Hussein, Y. R., Reis-Filho, J. S., Soslow, R. A., & Weigelt, B. (2015) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0000000000000243 · Cited by 134
Karnezis, A. N., Leung, S. C. Y., Magrill, J., McConechy, M. K., Yang, W., Chow, C., Köbel, M., Lee, C., Huntsman, D. D., Talhouk, A., et al. (2017) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.82 · Cited by 126
Self-citationMcCluggage, W. G., Soslow, R. A., & Gilks, C. B. (2011) · Histopathology · doi:10.1111/j.1365-2559.2011.03907.x · Cited by 93
Self-citationThe Diagnosis of Endometrial Carcinomas With Clear Cells by Gynecologic Pathologists
Fadare, O., Parkash, V., Dupont, W. D., Ács, G., Atkins, K. A., Irving, J. A., Pirog, E. C., Quade, B. J., Quddus, M. R., Rabban, J. T., et al. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e31825dd4b3 · Cited by 80
Immunohistochemical Profiling of Endometrial Serous Carcinoma
Chen, W., Husain, A., Nelson, G. S., Rambau, P., Liu, S., Lee, C., Lee, S., Duggan, M. A., & Köbel, M. (2016) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0000000000000291 · Cited by 62
Self-citationDavis, M., Rauh‐Hain, J. A., Andrade, C., Boruta, D. M., Schorge, J. O., Horowitz, N. S., May, T., & Carmen, M. G. D. (2014) · Gynecologic Oncology · doi:10.1016/j.ygyno.2014.01.012 · Cited by 58
Yano, M., Ito, K., Yabuno, A., Ogane, N., Katoh, T., Miyazawa, M., Miyazawa, M., Hasegawa, K., Narahara, H., & Yasuda, M. (2019) · Modern Pathology · doi:10.1038/s41379-019-0220-1 · Cited by 56
POLE proofreading mutation, immune response and prognosis in endometrial cancer
van Gool, I. C., Bosse, T., & Church, D. N. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1072675 · Cited by 43
Self-citationLee, S., Piskorz, A., Page, C. L., Mes‐Masson, A., Provencher, D. M., Huntsman, D. D., Chen, W., Swanson, P. E., Gilks, C. B., & Köbel, M. (2015) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0000000000000251 · Cited by 35
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Cited by
León-Castillo, A., de Boer, S. M., Powell, M. E., Mileshkin, L. R., Mackay, H. J., Leary, A., Nijman, H. W., Singh, N., Pollock, P. M., Bessette, P., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00549 · Cited by 855
Self-citationInterpretation of somatic POLE mutations in endometrial carcinoma
León‐Castillo, A., Britton, H., McConechy, M. K., McAlpine, J. N., Nout, R., Kommoss, S., Brucker, S. Y., Carlson, J. W., Epstein, E., Rau, T. T., et al. (2020) · The Journal of Pathology · doi:10.1002/path.5372 · Cited by 409
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Metadata
- Authors
- Singh, N., Piskorz, A. M., Bosse, T., Jimenez‐Linan, M., Rous, B., Brenton, J. D., Gilks, C. B., & Köbel, M.
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2020-01-29
- Volume
- 250
- Issue
- 3
- Pages
- 336-345
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2995292698
- Cited by
- 316
- References
- 32
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- closed
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