Skip to main content

Advertisement

SpringerLink
Log in

The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future

  • Review and Perspectives
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Karamanou M, Tsoucalas G, Laios K, Deligeoroglou E, Agapitos E, Androutsos G (2015) Uterine cancer in the writings of Byzantine physicians. J BUON 20(6):1645–1648

    PubMed  Google Scholar 

  2. Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15(1):10–17. https://doi.org/10.1016/0090-8258(83)90111-7

    Article  PubMed  CAS  Google Scholar 

  3. Lax SF, Pizer ES, Ronnett BM, Kurman RJ (1998) Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation. Hum Pathol 29(9):924–931. https://doi.org/10.1016/S0046-8177(98)90197-6

    Article  PubMed  CAS  Google Scholar 

  4. Soslow RA (2010) Endometrial carcinomas with ambiguous features. Semin Diagn Pathol 27(4):261–273. https://doi.org/10.1053/j.semdp.2010.09.003

    Article  PubMed  Google Scholar 

  5. Gilks CB, Oliva E, Soslow RA (2013) Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol 37(6):874–881. https://doi.org/10.1097/PAS.0b013e31827f576a

    Article  PubMed  Google Scholar 

  6. Lomo L, Nucci MR, Lee KR, Lin MC, Hirsch MS, Crum CP, Mutter GL (2008) Histologic and immunohistochemical decision-making in endometrial adenocarcinoma. Mod Pathol 21(8):937–942. https://doi.org/10.1038/modpathol.2008.97

    Article  PubMed  Google Scholar 

  7. Han G, Sidhu D, Duggan MA, Arseneau J, Cesari M, Clement PB, Ewanowich CA, Kalloger SE, Köbel M (2013) Reproducibility of histological cell type in high-grade endometrial carcinoma. Mod Pathol 26(12):1594–1604. https://doi.org/10.1038/modpathol.2013.102

    Article  PubMed  CAS  Google Scholar 

  8. Thomas S, Hussein Y, Bandyopadhyay S, Cote M, Hassan O, Abdulfatah E, Alosh B, Guan H, Soslow RA, Ali-Fehmi R (2016) Interobserver variability in the diagnosis of uterine high-grade endometrioid carcinoma. Arch Pathol Lab Med 140(8):836–843. https://doi.org/10.5858/arpa.2015-0220-OA

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kurman RJ, Carcangiu ML, Herrington CS, Young RH (2014) WHO classification of tumours of female reproducitve organs. International Agency for Research on Cancer, Lyon

    Google Scholar 

  10. Moreno-Bueno G, Sánchez-Estévez C, Cassia R, Rodríguez-Perales S, Díaz-Uriarte R, Domínguez O, Hardisson D, Andujar M, Prat J, Matias-Guiu X, Cigudosa JC, Palacios J (2003) Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 63(18):5697–5702

    PubMed  CAS  Google Scholar 

  11. Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, Reventos J, Palacios J, Prat J, Matias-Guiu X (2013) Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene 32(4):403–413. https://doi.org/10.1038/onc.2012.76

    Article  PubMed  CAS  Google Scholar 

  12. Garg K, Leitao MM, Wynveen CA, Sica GL, Shia J, Shi W, Soslow RA (2010) P53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes. Mod Pathol 23(1):80–92. https://doi.org/10.1038/modpathol.2009.153

    Article  PubMed  CAS  Google Scholar 

  13. Mackenzie R, Talhouk A, Eshragh S, Lau S, Cheung D, Chow C, Le N, Cook LS, Wilkinson N, McDermott J, Singh N, Kommoss F, Pfisterer J, Huntsman DG, Köbel M, Kommoss S, Gilks CB, Anglesio MS (2015) Morphological and molecular characteristics of mixed epithelial ovarian cancers. Am J Surg Pathol 39(11):1548–1557. https://doi.org/10.1097/PAS.0000000000000476

    Article  PubMed  PubMed Central  Google Scholar 

  14. Köbel M, Meng B, Hoang LN, Almadani N, Li X, Soslow RA, Gilks CB, Lee CH (2016) Molecular analysis of mixed endometrial carcinomas shows clonality in most cases. Am J Surg Pathol 40:166–180. https://doi.org/10.1097/PAS.0000000000000536

    Article  PubMed  PubMed Central  Google Scholar 

  15. Coenegrachts L, Garcia-Dios DA, Depreeuw J, Santacana M, Gatius S, Zikan M, Moerman P, Verbist L, Lambrechts D, Matias-Guiu X, Amant F (2015) Mutation profile and clinical outcome of mixed endometrioid-serous endometrial carcinomas are different from that of pure endometrioid or serous carcinomas. Virchows Arch 466(4):415–422. https://doi.org/10.1007/s00428-015-1728-5

    Article  PubMed  CAS  Google Scholar 

  16. Kurman RJ, Scully RE (1976) Clear cell carcinoma of the endometrium: an analysis of 21 cases. Cancer 37(2):872–882. https://doi.org/10.1002/1097-0142(197602)37:2<872::AID-CNCR2820370236>3.0.CO;2-L

    Article  PubMed  CAS  Google Scholar 

  17. Christopherson WM, Alberhasky RC, Connelly PJ (1982) Carcinoma of the endometrium: I. A clinicopathologic study of clear-cell carcinoma and secretory carcinoma. Cancer 49(8):1511–1523. https://doi.org/10.1002/1097-0142(19820415)49:8<1511::AID-CNCR2820490802>3.0.CO;2-6

    Article  PubMed  CAS  Google Scholar 

  18. Hendrickson M, Ross J, Eifel P, Martinez A, Kempson R (1982) Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma. Am J Surg Pathol 6(2):93–108. https://doi.org/10.1097/00000478-198203000-00002

    Article  PubMed  CAS  Google Scholar 

  19. Sato Y, Ozaki M, Ueda G, Tanizawa O (1985) A clinicopathologic study of endometrial carcinoma with special reference to new histological variants. Nihon Sanka Fujinka Gakkai Zasshi 37(6):1015–1019

    PubMed  CAS  Google Scholar 

  20. McGunigal M, Liu J, Kalir T, Chadha M, Gupta V (2017) Survival differences among uterine papillary serous, clear cell and grade 3 endometrioid adenocarcinoma endometrial cancers. Int J Gynecol Cancer 27(1):85–92. https://doi.org/10.1097/IGC.0000000000000844

    Article  PubMed  Google Scholar 

  21. Goto T, Takano M, Aoyama T, Miyamoto M, Watanabe A, Kato M, Sasaki N, Hirata J, Sasa H, Furuya K (2012) Prognosis of high-grade endometrial cancer: a comparison of serous-type and clear cell type to grade 3 endometrioid-type. Eur J Gynaecol Oncol 33(6):579–583

    PubMed  CAS  Google Scholar 

  22. Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, Powell MA, Hendrickson MR, Kapp DS, Chan JK (2006) Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer 94(5):642–646. https://doi.org/10.1038/sj.bjc.6603012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Boruta DM, Gehrig PA, Groben PA, Bae-Jump V, Boggess JF, Fowler WC, van le L (2004) Uterine serous and grade 3 endometrioid carcinomas: is there a survival difference? Cancer 101(10):2214–2221. https://doi.org/10.1002/cncr.20645

    Article  PubMed  Google Scholar 

  24. Soslow RA, Bissonnette JP, Wilton A, Ferguson SE, Alektiar KM, Duska LR, Oliva E (2007) Clinicopathologic analysis of 187 high-grade endometrial carcinomas of different histologic subtypes: similar outcomes belie distinctive biologic differences. Am J Surg Pathol 31(7):979–987. https://doi.org/10.1097/PAS.0b013e31802ee494

    Article  PubMed  Google Scholar 

  25. Voss MA, Ganesan R, Ludeman L, McCarthy K, Gornall R, Schaller G, Wei W, Sundar S (2012) Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer—a clinical and pathological evaluation. Gynecol Oncol 124(1):15–20. https://doi.org/10.1016/j.ygyno.2011.07.030

    Article  PubMed  Google Scholar 

  26. Alkushi A, Köbel M, Kalloger SE, Gilks CB (2010) High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes. Int J Gynecol Pathol 29(4):343–350. https://doi.org/10.1097/PGP.0b013e3181cd6552

    Article  PubMed  Google Scholar 

  27. Nicolini A, Ferrari P, Duffy MJ (2017) Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2017.08.010

  28. Kumar M, Ernani V, Owonikoko TK (2015) Biomarkers and targeted systemic therapies in advanced non-small cell lung cancer. Mol Asp Med 45:55–66. https://doi.org/10.1016/j.mam.2015.06.009

    Article  CAS  Google Scholar 

  29. Lax SF, Kendall B, Tashiro H, Slebos RJC, Ellenson LH (2000) The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer 88(4):814–824. https://doi.org/10.1002/(SICI)1097-0142(20000215)88:4<814::AID-CNCR12>3.0.CO;2-U

    Article  PubMed  CAS  Google Scholar 

  30. Mittal K, Soslow R, McCluggage WG (2008) Application of immunohistochemistry to gynecologic pathology. Arch Pathol Lab Med 132(3):402–423. https://doi.org/10.1043/1543-2165(2008)132[402:AOITGP]2.0.CO;2

    Article  PubMed  Google Scholar 

  31. Köbel M, Piskorz AM, Lee S, Lui S, LePage C, Marass F, Rosenfeld N, Mes Masson AM, Brenton JD (2016) Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res 2(4):247–258. https://doi.org/10.1002/cjp2.53

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Alkushi A, Clarke BA, Akbari M, Makretsov N, Lim P, Miller D, Magliocco A, Coldman A, van de Rijn M, Huntsman D, Parker R, Gilks CB (2007) Identification of prognostically relevant and reproducible subsets of endometrial adenocarcinoma based on clustering analysis of immunostaining data. Mod Pathol 20(11):1156–1165. https://doi.org/10.1038/modpathol.3800950

    Article  PubMed  CAS  Google Scholar 

  33. Wei J-J, Paintal A, Keh P (2013) Histologic and immunohistochemical analyses of endometrial carcinomas: experiences from endometrial biopsies in 358 consultation cases. Arch Pathol Lab Med 137(11):1574–1583. https://doi.org/10.5858/arpa.2012-0445-OA

    Article  PubMed  Google Scholar 

  34. Kapucuoglu N, Bulbul D, Tulunay G, Temel MA (2008) Reproducibility of grading systems for endometrial endometrioid carcinoma and their relation with pathologic prognostic parameters. Int J Gynecol Cancer 18(4):790–796. https://doi.org/10.1111/j.1525-1438.2007.01067.x

    Article  PubMed  CAS  Google Scholar 

  35. Yoon G, Won Koh C, Yoon N, Kim JY, Kim HS (2017) Stromal p16 expression is significantly increased in endometrial carcinoma. Oncotarget. https://doi.org/10.18632/oncotarget.13594

  36. McCluggage WG, Jenkins D (2003) p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol 22(3):231–235. https://doi.org/10.1097/01.PGP.0000055172.04957.2F

    Article  PubMed  CAS  Google Scholar 

  37. Chekmareva M, Ellenson LH, Pirog EC (2008) Immunohistochemical differences between mucinous and microglandular adenocarcinomas of the endometrium and benign endocervical epithelium. Int J Gynecol Pathol 27(4):547–554. https://doi.org/10.1097/PGP.0b013e318177

    Article  PubMed  Google Scholar 

  38. Fadare O, Desouki MM, Gwin K, Hanley KZ, Jarboe EA, Liang SX, Quick CM, Zheng W, Parkash V, Hecht JL (2014) Frequent expression of napsin A in clear cell carcinoma of the endometrium: potential diagnostic utility. Am J Surg Pathol 38(2):189–196. https://doi.org/10.1097/PAS.0000000000000085

    Article  PubMed  Google Scholar 

  39. Hoang LN, McConechy MK, Meng B, McIntyre JB, Ewanowich C, Gilks CB, Huntsman DG, Köbel M, Lee CH (2015) Targeted mutation analysis of endometrial clear cell carcinoma. Histopathology 66(5):664–674. https://doi.org/10.1111/his.12581

    Article  PubMed  Google Scholar 

  40. Al-Maghrabi JA, Butt NS, Anfinan N, Sait K, Sait H, Marzouki A, Khabaz MN (2016) Infrequent immunohistochemical expression of napsin A in endometrial carcinomas. Appl Immunohistochem Mol Morphol 1(9):632–638. https://doi.org/10.1097/PAI.0000000000000350

    Article  CAS  Google Scholar 

  41. Stewart CJR, Crook ML (2015) SWI/SNF complex deficiency and mismatch repair protein expression in undifferentiated and dedifferentiated endometrial carcinoma. Pathology 47(5):439–445. https://doi.org/10.1097/PAT.0000000000000270

    Article  PubMed  CAS  Google Scholar 

  42. Hoang LN, Lee Y-S, Karnezis AN, Tessier-Cloutier B, Almandani N, Coatham M, Gilks CB, Soslow RA, Stewart CJR, Köbel M, Lee CH (2016) Immunophenotypic features of dedifferentiated endometrial carcinoma—insights from BRG1/INI1-deficient tumours. Histopathology 69(4):560–569. https://doi.org/10.1111/his.12989

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ramalingam P, Croce S, McCluggage WG (2017) Loss of expression of SMARCA4 (BRG1), SMARCA2 (BRM) and SMARCB1 (INI1) in undifferentiated carcinoma of the endometrium is not uncommon and is not always associated with rhabdoid morphology. Histopathology 70(3):359–366. https://doi.org/10.1111/his.13091

    Article  PubMed  Google Scholar 

  44. Karnezis AN, Hoang LN, Coatham M, Ravn S, Almadani N, Tessier-Cloutier B, Irving J, Meng B, Li X, Chow C, McAlpine J, Kuo KT, Mao TL, Djordjevic B, Soslow RA, Huntsman DG, Blake Gilks C, Köbel M, Lee CH (2016) Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas. Mod Pathol 29(3):302–314. https://doi.org/10.1038/modpathol.2015.155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Ramalingam P, Masand RP, Euscher ED, Malpica A (2016) Undifferentiated carcinoma of the endometrium: an expanded immunohistochemical analysis including PAX-8 and basal-like carcinoma surrogate markers. Int J Gynecol Pathol 35(5):410–418. https://doi.org/10.1097/PGP.0000000000000248

    Article  PubMed  CAS  Google Scholar 

  46. Li Z, Zhao C (2016) Clinicopathologic and immunohistochemical characterization of dedifferentiated endometrioid adenocarcinoma. Appl Immunohistochem Mol Morphol AIMM 24(8):562–568. https://doi.org/10.1097/PAI.0000000000000232

    Article  PubMed  CAS  Google Scholar 

  47. Djordjevic B, Hennessy BT, Li J, Barkoh BA, Luthra R, Mills GB, Broaddus RR (2012) Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. Mod Pathol 25(5):699–708. https://doi.org/10.1038/modpathol.2011.208

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Maiques O, Santacana M, Valls J, Pallares J, Mirantes C, Gatius S, García Dios d, Amant F, Pedersen HC, Dolcet X, Matias-Guiu X (2014) Optimal protocol for PTEN immunostaining; role of analytical and preanalytical variables in PTEN staining in normal and neoplastic endometrial, breast, and prostatic tissues. Hum Pathol 45(3):522–532. https://doi.org/10.1016/j.humpath.2013.10.018

    Article  PubMed  Google Scholar 

  49. Hoang LN, McConechy MK, Köbel M, Han G, Rouzbahman M, Davidson B, Irving J, Ali RH, Leung S, McAlpine JN, Oliva E, Nucci MR, Soslow RA, Huntsman DG, Gilks CB, Lee CH (2013) Histotype-genotype correlation in 36 high-grade endometrial carcinomas. Am J Surg Pathol 37(9):1421–1432. https://doi.org/10.1097/PAS.0b013e31828c63ed

    Article  PubMed  Google Scholar 

  50. Nastic D, Shanwell E, Wallin K-L, Valla M, Måsbäck A, Mateoiu C, Lidang M, Liakka A, Lappi-Blanco E, Grove A, Davidson B, Carpen O, Bertelsen BI, Bak J, Abusland AB, Selling J, Carlson JW (2017) A selective biomarker panel increases the reproducibility and the accuracy in endometrial biopsy diagnosis. Int J Gynecol Pathol 36(4):339–347. https://doi.org/10.1097/PGP.0000000000000334

    Article  PubMed  Google Scholar 

  51. Santacana M, Maiques O, Valls J, Gatius S, Abó AI, López-García MÁ, Mota A, Reventós J, Moreno-Bueno G, Palacios J, Bartosch C, Dolcet X, Matias-Guiu X (2014) A 9-protein biomarker molecular signature for predicting histologic type in endometrial carcinoma by immunohistochemistry. Hum Pathol 45(12):2394–2403. https://doi.org/10.1016/j.humpath.2014.06.031

    Article  PubMed  CAS  Google Scholar 

  52. McConechy MK, Ding J, Cheang MCU, Wiegand KC, Senz J, Tone AA, Yang W, Prentice LM, Tse K, Zeng T, McDonald H, Schmidt AP, Mutch DG, McAlpine JN, Hirst M, Shah SP, Lee CH, Goodfellow PJ, Gilks CB, Huntsman DG (2012) Use of mutation profiles to refine the classification of endometrial carcinomas. J Pathol 228:20–30. https://doi.org/10.1002/path.4056

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Guan B, Mao T-L, Panuganti PK, Kuhn E, Kurman RJ, Maeda D, Chen E, Jeng YM, Wang TL, Shih IM (2011) Mutation and loss of expression of ARID1A in uterine low-grade endometrioid carcinoma. Am J Surg Pathol 35(5):625–632. https://doi.org/10.1097/PAS.0b013e318212782a

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hoang LN, Han G, McConechy M, Lau S, Chow C, Gilks CB, Huntsman DG, Köbel M, Lee CH (2014) Immunohistochemical characterization of prototypical endometrial clear cell carcinoma—diagnostic utility of HNF-1β and oestrogen receptor. Histopathology 64(4):585–596. https://doi.org/10.1111/his.12286

    Article  PubMed  Google Scholar 

  55. Cancer Genome Atlas Research Network T (2013) Integrated genomic characterization of endometrial carcinoma. doi: https://doi.org/10.1038/nature12113

  56. Oda K, Stokoe D, Taketani Y, McCormick F (2005) High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res 65(23):10669–10673. https://doi.org/10.1158/0008-5472.CAN-05-2620

    Article  PubMed  CAS  Google Scholar 

  57. Rudd ML, Price JC, Fogoros S, Godwin AK, Sgroi DC, Merino MJ, Bell DW (2011) A unique spectrum of somatic PIK3CA (p110 ) mutations within primary endometrial carcinomas. Clin Cancer Res 17(6):1331–1340. https://doi.org/10.1158/1078-0432.CCR-10-0540

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Gatius S, Matias-Guiu X (2016) Practical issues in the diagnosis of serous carcinoma of the endometrium. Mod Pathol 29:S45–S58. https://doi.org/10.1038/modpathol.2015.141

    Article  PubMed  CAS  Google Scholar 

  59. Schultheis AM, Martelotto LG, De Filippo MR, Piscuglio S, Ng CKY, Hussein YR, Reis-Filho JS, Soslow RA, Weigelt B (2016) TP53 mutational spectrum in endometrioid and serous endometrial cancers. Int J Gynecol Pathol 35(4):289–300. https://doi.org/10.1097/PGP.0000000000000243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. McConechy MK, Anglesio MS, Kalloger SE, Yang W, Senz J, Chow C, Heravi-Moussavi A, Morin GB, Mes-Masson AM, Australian Ovarian Cancer Study Group, Carey MS, McAlpine JN, Kwon JS, Prentice LM, Boyd N, Shah SP, Gilks CB, Huntsman DG (2011) Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. J Pathol 223(5):567–573. https://doi.org/10.1002/path.2848

    Article  PubMed  CAS  Google Scholar 

  61. Singh N, Gilks CB, Gilks SN (2017) The changing landscape of gynaecological cancer diagnosis: implications for histopathological practice in the 21st century. Histopathology 70(1):56–69. https://doi.org/10.1111/his.13080

    Article  PubMed  Google Scholar 

  62. Hoang LN, Kinloch MA, Leo JM, Grondin K, Lee CH, Ewanowich C, Köbel M, Cheng A, Talhouk A, McConechy M, Huntsman DG, McAlpine JN, Soslow RA, Gilks CB (2017) Interobserver agreement in endometrial carcinoma histotype diagnosis varies depending on The Cancer Genome Atlas (TCGA)-based molecular subgroup. Am J Surg Pathol 41(2):245–252. https://doi.org/10.1097/PAS.0000000000000764

    Article  PubMed  Google Scholar 

  63. Mota A, Colás E, García-Sanz P, Campoy I, Rojo-Sebastián A, Gatius S, García Á, Chiva L, Alonso S, Gil-Moreno A, González-Tallada X, Díaz-Feijoo B, Vidal A, Ziober-Malinowska P, Bobiński M, López-López R, Abal M, Reventós J, Matias-Guiu X, Moreno-Bueno G (2017) Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers. Mod Pathol 30(1):134–145. https://doi.org/10.1038/modpathol.2016.143

    Article  PubMed  CAS  Google Scholar 

  64. Stelloo E, Nout RA, Osse EM, Jürgenliemk-Schulz IJ, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Nijman HW, Putter H, Bosse T, Creutzberg CL, Smit VTHBM (2016) Improved risk assessment by integrating molecular and clinicopathological factors in early-stage endometrial cancer-combined analysis of the PORTEC cohorts. Clin Cancer Res 22(16):4215–4224. https://doi.org/10.1158/1078-0432.CCR-15-2878

    Article  PubMed  CAS  Google Scholar 

  65. Bakhsh S, Kinloch M, Hoang LN, Soslow RA, Köbel M, Lee CH, McAlpine JN, McConechy MK, Gilks CB (2016) Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy. Histopathology 68(6):916–924. https://doi.org/10.1111/his.12878

    Article  PubMed  Google Scholar 

  66. McConechy MK, Talhouk A, Leung S, Chiu D, Yang W, Senz J, Reha-Krantz LJ, Lee CH, Huntsman DG, Gilks CB, McAlpine JN (2016) Endometrial carcinomas with POLE exonuclease domain mutations have a favorable prognosis. Clin Cancer Res 22(12):2865–2873. https://doi.org/10.1158/1078-0432.CCR-15-2233

    Article  PubMed  CAS  Google Scholar 

  67. Church DN, Stelloo E, Nout RA, Valtcheva N, Depreeuw J, ter Haar N, Noske A, Amant F, Tomlinson IPM, Wild PJ, Lambrechts D, Jürgenliemk-Schulz IM, Jobsen JJ, Smit VTHBM, Creutzberg CL, Bosse T (2015) Prognostic significance of POLE proofreading mutations in endometrial cancer. J Natl Cancer Inst 107(1):402. https://doi.org/10.1093/jnci/dju402

    Article  PubMed  CAS  Google Scholar 

  68. Shikama A, Minaguchi T, Matsumoto K, Akiyama-Abe A, Nakamura Y, Michikami H, Nakao S, Sakurai M, Ochi H, Onuki M, Satoh T, Oki A, Yoshikawa H (2016) Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas. Gynecol Oncol 140(2):226–233. https://doi.org/10.1016/j.ygyno.2015.11.032

    Article  PubMed  CAS  Google Scholar 

  69. Garg K, Soslow RA (2009) Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma. J Clin Pathol 62(8):679–684. https://doi.org/10.1136/jcp.2009.064949

    Article  PubMed  CAS  Google Scholar 

  70. Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, Yang W, Senz J, Boyd N, Karnezis AN, Huntsman DG, Gilks CB, McAlpine JN (2015) A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 113(2):299–310. https://doi.org/10.1038/bjc.2015.190

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, Boyd N, Pike J, Anglesio M, Kwon JS, Karnezis AN, Huntsman DG, Gilks CB, McAlpine JN (2017) Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 123(5):802–813. https://doi.org/10.1002/cncr.30496

    Article  PubMed  CAS  Google Scholar 

  72. McConechy MK, Talhouk A, Li-Chang HH, Leung S, Huntsman DG, Gilks CB, McAlpine JN (2015) Detection of DNA mismatch repair (MMR) deficiencies by immunohistochemistry can effectively diagnose the microsatellite instability (MSI) phenotype in endometrial carcinomas. Gynecol Oncol 137(2):306–310. https://doi.org/10.1016/j.ygyno.2015.01.541

    Article  PubMed  CAS  Google Scholar 

  73. Talhouk A, Hoang LN, McConechy MK, Nakonechny Q, Leo J, Cheng A, Leung S, Yang W, Lum A, Köbel M, Lee CH, Soslow RA, Huntsman DG, Gilks CB, McAlpine JN (2016) Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: earlier prognostic information to guide treatment. Gynecol Oncol 143(1):46–53. https://doi.org/10.1016/j.ygyno.2016.07.090

    Article  PubMed  PubMed Central  Google Scholar 

  74. Lee S, Piskorz AM, Le Page C, Mes Masson AM, Provencher D, Huntsman D, Chen W, Swanson PE, Gilks CB, Köbel M (2016) Calibration and optimization of p53, WT1, and napsin A immunohistochemistry ancillary tests for histotyping of ovarian carcinoma: Canadian Immunohistochemistry Quality Control (CIQC) experience. Int J Gynecol Pathol 35(3):209–221. https://doi.org/10.1097/PGP.0000000000000251

    Article  PubMed  CAS  Google Scholar 

  75. Piulats JM, Matias-Guiu X (2016) Immunotherapy in endometrial cancer: in the nick of time. Clin Cancer Res 22(23):5623–5625. https://doi.org/10.1158/1078-0432.CCR-16-1820

    Article  PubMed  CAS  Google Scholar 

  76. Piulats JM, Guerra E, Gil-Martín M, Roman-Canal B, Gatius S, Sanz-Pamplona R, Velasco A, Vidal A, Matias-Guiu X (2017) Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol 145(1):200–207. https://doi.org/10.1016/j.ygyno.2016.12.015

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Xavier Matias-Guiu and C. Blake Gilks contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada

    Emily A. Goebel

  2. Hospital Universitari de Bellvitge, IDIBELL, CIBERONC, L’Hospitalet de Llobregat, Barcelona, Spain

    August Vidal

  3. Department of Pathology, Hospital Universitari Arnau de Vilanova de Lleida and Hospital Universitari de Bellvitge, IRBLleida, IDIBELL, CIBERONC, L’Hospitalet de Llobregat, Barcelona, Spain

    Xavier Matias-Guiu

  4. Department of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada

    C. Blake Gilks

Authors
  1. Emily A. Goebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. August Vidal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xavier Matias-Guiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Blake Gilks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Blake Gilks.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goebel, E.A., Vidal, A., Matias-Guiu, X. et al. The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future. Virchows Arch 472, 885–896 (2018). https://doi.org/10.1007/s00428-017-2279-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2279-8

Keywords

Search

Navigation