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Controversies in Pathology and Advances in Molecular Diagnostics

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Management of Endometrial Cancer

Abstract

Pathology is an evolving specialty, and the advancement of knowledge has led to the introduction of new concepts and diagnoses, and the disappearance of others. Just as in clinical medicine, the evolution of the field is rarely due to presence of perfect data. Classification systems evolve and adapt, with the integration of new discoveries. This is particularly true of endometrial cancer, where a number of new molecular factors have been identified in the past few years.

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References

  1. Kurman RJ, Carcangiu ML, Herrington CS, Roung RH, IARC. WHO classification of tumours of female reproductive organs. Lyon: IARC Press; 2014.

    Google Scholar 

  2. Zaino RJ, Kauderer J, Trimble CL, Silverberg SG, Curtin JP, Lim PC, Gallup DG, Mackey D. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a gynecologic oncology group study. Cancer. 2006;106(4):804–11. https://doi.org/10.1002/cncr.21649.

    Article  PubMed  Google Scholar 

  3. ACOG. Endometrial Intraepithelial Neoplasia Committee Opinion No. 631. 2015.

    Google Scholar 

  4. Owings RA, Quick CM. Endometrial intraepithelial neoplasia. Arch Pathol Lab Med. 2014;138(4):484–91. https://doi.org/10.5858/arpa.2012-0709-RA.

    Article  PubMed  Google Scholar 

  5. Malpica A. How to approach the many faces of endometrioid carcinoma. Mod Pathol. 2016;29(S1):S29–44. https://doi.org/10.1038/modpathol.2015.142.

    Article  CAS  PubMed  Google Scholar 

  6. FIGO. Announcements. Gynecol Oncol. 1989;35(1):125–7. https://doi.org/10.1016/0090-8258(89)90027-9.

    Article  Google Scholar 

  7. Alkushi A, Abdul-Rahman ZH, Lim P, Schulzer M, Coldman A, Kalloger SE, Miller D, Gilks CB. Description of a novel system for grading of endometrial carcinoma and comparison with existing grading systems. Am J Surg Pathol. 2005;29(3):295–304. https://doi.org/10.1097/01.pas.0000152129.81363.d2.

    Article  PubMed  Google Scholar 

  8. Gatius S, Matias-guiu X. Practical issues in the diagnosis of serous carcinoma of the endometrium. Mod Pathol. 2016;29(S1):S45–58. https://doi.org/10.1038/modpathol.2015.141.

    Article  CAS  PubMed  Google Scholar 

  9. Soslow RA. Endometrial carcinomas with ambiguous features. Semin Diagn Pathol. 2010;27:261–73. https://doi.org/10.1053/j.semdp.2010.09.003.

    Article  PubMed  Google Scholar 

  10. Colombo N, Creutzberg C, Amant F, Bosse T, González-Martín A, Ledermann J, Marth C, et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol. 2016;27(1):16–41. https://doi.org/10.1093/annonc/mdv484.

    Article  CAS  PubMed  Google Scholar 

  11. Cole AJ, Quick CM. Patterns of myoinvasion in endometrial adenocarcinoma: recognition and implications. Adv Anat Pathol. 2013;20(3):141–7. https://doi.org/10.1097/PAP.0b013e31828d17cc.

    Article  CAS  PubMed  Google Scholar 

  12. Hui P, Kelly M, O’Malley DM, Tavassoli F, Schwartz PE. Minimal uterine serous carcinoma: a clinicopathological study of 40 cases. Mod Pathol. 2005;18(1):75–82. https://doi.org/10.1038/modpathol.3800271.

    Article  PubMed  Google Scholar 

  13. Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine serous carcinoma. A morphologically diverse neoplasm with unifying clinicopathologic features. Am J Surg Pathol. 1992;16(6):600–10.

    Article  CAS  PubMed  Google Scholar 

  14. Köbel M, Piskorz AM, Lee S, Lui S, LePage C, Marass F, Rosenfeld N, Mes Masson A-M, Brenton JD. Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res. 2016;2(4):247–58. https://doi.org/10.1002/cjp2.53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lavie O, Ben-Arie A, Segev Y, Faro J, Barak F, Haya N, Auslender R, Gemer O. BRCA germline mutations in women with uterine serous carcinoma--still a debate. Int J Gynecol Cancer. 2010;20(9):1531–4. https://doi.org/10.1111/IGC.0b013e3181cd242f.

    Article  PubMed  Google Scholar 

  16. Fadare O, Zheng W, Crispens M a, Jones HWI, Khabele D, Gwin K, Liang SX, et al. Morphologic and other clinicopathologic features of endometrial clear cell carcinoma: a comprehensive analysis of 50 rigorously classified cases. Am J Cancer Res. 2013;3(1):70–95.

    PubMed  PubMed Central  Google Scholar 

  17. Fadare O, Desouki MM, Gwin K, Hanley KZ, Jarboe EA, Liang SX, Quick CM, Zheng W, Parkash V, Hecht JL. Frequent expression of napsin A in clear cell carcinoma of the endometrium: potential diagnostic utility. Am J Surg Pathol. 2014;38(2):189–96. https://doi.org/10.1097/PAS.0000000000000085.

    Article  PubMed  Google Scholar 

  18. Fadare O, Gwin K, Desouki MM, Crispens MA, Jones HW, Khabele D, Liang SX, et al. The clinicopathologic significance of p53 and BAF-250a (ARID1A) expression in clear cell carcinoma of the Endometrium. Mod Pathol. 2013;26(8):1101–10. https://doi.org/10.1038/modpathol.2013.35.

    Article  CAS  PubMed  Google Scholar 

  19. Hoang LN, Mcconechy MK, Meng B, Mcintyre JB, Ewanowich C, Gilks CB, Huntsman DG, Köbel M, Lee CH. Targeted mutation analysis of endometrial clear cell carcinoma. Histopathology. 2015;66(5):664–74. https://doi.org/10.1111/his.12581.

    Article  PubMed  Google Scholar 

  20. Quddus M, Ruhul CJS, Zhang C, Dwayne Lawrence W. Minor serous and clear cell components adversely affect prognosis in mixed-type endometrial carcinomas: a clinicopathologic study of 36 stage-I cases. Reprod Sci. 2010;17(7):673–8. https://doi.org/10.1177/1933719110368433.

    Article  PubMed  Google Scholar 

  21. Cherniack AD, Shen H, Walter V, Stewart C, Murray BA, Bowlby R, Hu X, et al. Integrated molecular characterization of uterine carcinosarcoma. Cancer Cell. 2017;31(3):411–23. https://doi.org/10.1016/j.ccell.2017.02.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Network, Cancer Genome Atlas Reserach. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(53):67–73. https://doi.org/10.1038/nature12113.

    Article  CAS  Google Scholar 

  23. Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, et al. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecol Oncol. 2017;144(1):146–52. https://doi.org/10.1016/j.ygyno.2016.11.023.

    Article  CAS  PubMed  Google Scholar 

  24. Billingsley CC, Cohn DE, Mutch DG, Stephens JA, Suarez AA, Goodfellow PJ. Polymerase?? (POLE) mutations in endometrial cancer: clinical outcomes and implications for lynch syndrome testing. Cancer. 2015;121(3):386–94. https://doi.org/10.1002/cncr.29046.

    Article  CAS  PubMed  Google Scholar 

  25. Church DN, Briggs SEW, Palles C, Enric Domingo SJ, Kearsey JM, Grimes MG, et al. DNA polymerase {varepsilon} and δ exonuclease domain mutations in endometrial cancer. Hum Mol Genet. 2013;22(14):2820–8. https://doi.org/10.1093/hmg/ddt131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hussein YR, Britta Weigelt DA, Levine JKS, Dao LN, Balzer BL, Liles G, et al. Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Mod Pathol. 2015;28(4):505–14. https://doi.org/10.1038/modpathol.2014.143.

    Article  CAS  PubMed  Google Scholar 

  27. Meng B, Hoang LN, McIntyre JB, Duggan MA, Nelson GS, Lee CH, Köbel M. POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium. Gynecol Oncol. 2014;134(1):15–9. https://doi.org/10.1016/j.ygyno.2014.05.006.

    Article  CAS  PubMed  Google Scholar 

  28. Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of chemotherapy-resistant polymerase ε (POLE) ultra-mutated and MSH6 hyper-mutated endometrial tumors with nivolumab. Clin Cancer Res. 2016;22(23):5682–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bellone S, Centritto F, Black J, Schwab C, English D, Cocco E, Lopez S, et al. Polymerase?? (POLE) ultra-mutated tumors induce robust tumor-specific CD4 + T cell responses in endometrial cancer patients. Gynecol Oncol. 2015;138(1):11–7. https://doi.org/10.1016/j.ygyno.2015.04.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Eggink FA, Van Gool IC, Leary A, Pollock PM, Crosbie EJ, Mileshkin L, Jordanova ES, et al. Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE -mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition. OncoImmunology. 2017;6(2):e1264565. https://doi.org/10.1080/2162402X.2016.1264565.

    Article  CAS  PubMed  Google Scholar 

  31. Van Gool IC, Eggink FA, Freeman-Mills L, Stelloo E, Marchi E, De Bruyn M, Palles C, et al. POLE proofreading mutations elicit an antitumor immune response in endometrial cancer. Clin Cancer Res. 2015;21(14):3347–55. https://doi.org/10.1158/1078-0432.CCR-15-0057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mehnert JM, Panda A, Zhong H, Hirshfield K, Damare S, Lane K, Sokol L, et al. Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Investig. 2016;126(6):2334–40. https://doi.org/10.1172/JCI84940.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jarboe E, Folkins A, Nucci MR, Kindelberger D, Drapkin R, Miron A, Lee Y, Crum CP. Serous carcinogenesis in the fallopian tube. Int J Gynecol Pathol. 2008;27(1):1–9. https://doi.org/10.1097/pgp.0b013e31814b191f.

    Article  PubMed  Google Scholar 

  34. Talhouk A, McAlpine JN. New classification of endometrial cancers: The development and potential applications of genomic-based classification in research and clinical care. Gynecol Oncol Res Pract. 2016;3(1):14. https://doi.org/10.1186/s40661-016-0035-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, Yang W, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015;113(2):299–310. https://doi.org/10.1038/bjc.2015.190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Stelloo E, Nout RAA, Osse EMM, rgenliemk-Schulz IJJ, Jobsen JJJ, Lutgens LCC, van der Steen-Banasik EMM, et al. Improved risk assessment by integrating molecular and clinicopathological factors in early-stage endometrial cancer - combined analysis of PORTEC cohorts. Clin Cancer Res. 2016;22(16):4215. https://doi.org/10.1158/1078-0432.CCR-15-2878.

    Article  CAS  PubMed  Google Scholar 

  37. Stelloo E, Bosse T, Nout RA, MacKay HJ, Church DN, Nijman HW, Leary A, et al. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol. 2015;28(6):836–44. https://doi.org/10.1038/modpathol.2015.43.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Joseph W. Carlson .

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Imboden, S., Nastic, D., Carlson, J.W. (2020). Controversies in Pathology and Advances in Molecular Diagnostics. In: Mirza, M. (eds) Management of Endometrial Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-64513-1_2

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  • DOI: https://doi.org/10.1007/978-3-319-64513-1_2

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