Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Endometrial carcinoma: molecular alterations involved in tumor development and progression

Oncogene volume 32, pages 403–413 (2013)Cite this article

Subjects

Abstract

In the western world, endometrial carcinoma (EC) is the most common cancer of the female genital tract. The annual incidence has been estimated at 10–20 per 100 000 women. Two clinicopathological variants are recognized: the estrogen related (type I, endometrioid) and the non-estrogen related (type II, non-endometrioid).The clinicopathological differences are paralleled by specific genetic alterations, with type I showing microsatellite instability and mutations in phosphatase and tensin homologue deleted on chromosome 10, PIK3CA, K-RAS and CTNNB1 (β-catenin), and type II exhibiting TP53 mutations and chromosomal instability. Some non-endometrioid carcinomas probably arise from pre-existing endometrioid carcinomas as a result of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological and molecular levels. In EC, apoptosis resistance may have a role in tumor progression. Understanding pathogenesis at the molecular level is essential in identifying biomarkers for successful targeted therapies. In this review, the genetic changes of endometrial carcinogenesis are discussed in the light of the morphological features of the tumors and their precursors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Bokhman JV . Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15: 10–17.

    CAS  PubMed  Google Scholar 

  2. Matias-Guiu X, Catasús L, Bussaglia E, Lagarda H, Garcia A, Pons C et al. Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 2001; 32: 569–577.

    CAS  PubMed  Google Scholar 

  3. Prat J, Gallardo A, Cuatrecasas M, Catasús L . Endometrial carcinoma: pathology and genetics. Pathology 2007; 39: 72–87.

    CAS  PubMed  Google Scholar 

  4. Llobet D, Pallares J, Yeramian A, Santacana M, Eritja N, Velasco A et al. Molecular pathology of endometrial carcinoma; practical aspects from the diagnostic and therapeutical view points. J Clin Pathol 2009; 62: 777–785.

    CAS  PubMed  Google Scholar 

  5. Duggan BD, Felix JC, Muderspach LI, Tourgeman D, Zheng J, Shibata D . Microsatellite instability in sporadic endometrial carcinoma. J Natl Cancer Inst 1994; 86: 1216–1221.

    CAS  PubMed  Google Scholar 

  6. Kobayashi K, Sagae S, Kudo H, Koi S, Nakamura Y . Microsatellite instability in endometrial carcinomas: frequent replication errors in tumors of early onset and/or of poorly differentiated type. Genes Chromosom Cancer 1995; 14: 128–132.

    CAS  PubMed  Google Scholar 

  7. Risinger JI, Berchuck A, Kohler MF, Watson P, Lynch HT, Boyd J . Genetic instability of microsatellites in endometrial carcinoma. Cancer Res 1993; 53: 5100–5103.

    CAS  PubMed  Google Scholar 

  8. Catasús L, Machin P, Matias-Guiu X, Prat J . Microsatellite instability in endometrial carcinomas clinicopathologic correlations in a series of 42 cases. Human Pathol 1998; 29: 1160–1164.

    Google Scholar 

  9. Esteller M, Catasús Ll, Matias-Guiu X, Mutter GL, Prat J, Baylin SB et al. hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 1999; 155: 1767–1772.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Catasús L, Matias-Guiu X, Machin P, Muñoz J, Prat J . BAX somatic framshift mutations in endometrioid adenocarcinomas of the endometrium: evidence for a tumor progression role in endometrioid carcinomas with microsatellite instability. Lab Invest 1998; 78: 1439–1444.

    PubMed  Google Scholar 

  11. Catasús L, Matias-Guiu X, Machin P, Zannoni GF, Scambia G, Benedetti Panici PL et al. Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinomas with microsatellite instability. Cancer 2000; 88: 2290–2297.

    PubMed  Google Scholar 

  12. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000; 92: 924–931.

    CAS  PubMed  Google Scholar 

  13. Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 1997; 57: 3935–3940.

    CAS  PubMed  Google Scholar 

  14. Bussaglia E, del Rio E, Matias-Guiu X, Prat J . PTEN mutations in endometrial carcinomas. A molecular and clinicopathologic analysis of 38 cases. Hum Pathol 2000; 31: 312–317.

    CAS  PubMed  Google Scholar 

  15. Nagase S, Sato S, Tezuka F, Wada Y, Yajima A, Horii A . Deletion mapping on chromosome 10q25-q26 in human endometrial cancer. Br J Cancer 1996; 74: 1979–1983.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 2007; 128: 157–170.

    CAS  PubMed  Google Scholar 

  17. Dedes KJ, Wetterskog D, Mendes-Pereira AM, Natrajan R, Lambros MB, Geyer FC et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci Transl Med 2010; 2: 53ra75.

    PubMed  Google Scholar 

  18. Oda K, Stokoe D, Taketani Y, McCormick F . High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res 2005; 65: 10669–10673.

    CAS  PubMed  Google Scholar 

  19. Velasco A, Bussaglia E, Pallares J, Dolcet X, Llobet D, Encinas M et al. PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. Hum Pathol 2006; 37: 1465–1472.

    CAS  PubMed  Google Scholar 

  20. Catasús L, Gallardo A, Cuatrecasas M, Prat J . PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod Pathol 2008; 21: 131–139.

    PubMed  Google Scholar 

  21. Rudd ML, Price JC, Fogoros S, Godwin AK, Sgroi DC, Merino MJ et al. A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res 2011; 17: 1331–1340.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Catasús L, Gallardo A, Cuatrecasas M, Prat J . Concomitant PI3K-AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis. Mod Pathol 2009; 22: 522–529.

    PubMed  Google Scholar 

  23. Hayes MP, Douglas W, Ellenson LH . Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. Gynecol Oncol 2009; 113: 370–373.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Catasús L, D’Angelo E, Pons C, Espinosa I, Prat J . Expression profiling of 22 genes involved in the PI3K-AKT pathway identifies two subgroups of high-grade endometrial carcinomas with different molecular alterations. Mod Pathol 2010; 23: 694–702.

    PubMed  Google Scholar 

  25. Urick ME, Rudd ML, Godwin AK, Sgroi D, Merino M . Bell DW PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res 2011; 71: 4061–4067.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Milam MR, Celestino J, Wu W, Broaddus RR, Schmeler KM, Slomovitz BM et al. Reduced progression of endometrial hyperplasia with oral mTOR inhibition in the Pten heterozygote murine model. Am J Obstet Gynecol 2007; 196: 247.e1–5.

    PubMed  Google Scholar 

  27. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008; 68: 8022–8030.

    Article  CAS  PubMed  Google Scholar 

  28. Lagarda H, Catasús L, Argüelles R, Matias-Guiu X, Prat J . K-ras mutations in endometrial carcinoma with microsatellite instabilit. J Pathol 2001; 193: 193–199.

    CAS  PubMed  Google Scholar 

  29. Moreno-Bueno G, Sanchez-Estevez C, Palacios J, Hardisson D, Shiozawa T . frequency of BRAF mutations in endometrial and in cervical carcinomas. Clin Cancer Res 2006; 12: 3865.

    CAS  PubMed  Google Scholar 

  30. Pallarés J, Velasco A, Eritja N, Santacana M, Dolcet X, Cuatrecasas M et al. hypermethylation and reduced expression of RASSF1A are frequent molecular alterations of endometrial carcinoma. Mod Pathol 2008; 21: 691–699.

    PubMed  Google Scholar 

  31. Velasco A, Pallares J, Santacana M, Gatius S, Fernandez M, Domingo M et al. Promoter hypermethylation and expression of sprouty 2 in endometrial carcinoma. Hum Pathol 2011; 42: 185–193.

    CAS  PubMed  Google Scholar 

  32. Pollock PM, Gartside MG, Dejeza LC, Powell MA, Mallon MA, Mohammadi M et al. Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. Oncogene 2007; 26: 7158–7162.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci USA 2008; 105: 8713–8717.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Gatius S, Velasco A, Azueta A, Santacana M, Pallares J, Valls J et al. FGFR-2 alterations in endometrial carcinoma. Mod Pathol 2011; 24: 1500–1510.

    CAS  PubMed  Google Scholar 

  35. Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S, Hirohashi S . Beta-catenin mutations in carcinoma of the uterine endometrium. Cancer Res 1998; 58: 3526–3528.

    CAS  PubMed  Google Scholar 

  36. Kobayashi K, Sagae S, Nishioka Y, Tokino T, Kudo R . Mutations of the beta-catenin gene in endometrial carcinomas. Jpn J Cancer Res 1999; 90: 55–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Machin P, Catasús L, Pons C, Muñoz J, Matias-Guiu X, Prat J . CTNNB1 mutations and beta-catenin expression in endometrial carcinomas. Human Pathol 2002; 33: 206–212.

    CAS  Google Scholar 

  38. Palacios J, Moreno-Bueno G, Catasús L, Matias-Guiu X, Prat J, Gamallo C . Beta and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability. Virchows Arch 2001; 193: 193–199.

    Google Scholar 

  39. Moreno-Bueno G, Hardisson D, Sánchez C, Sarrió D, Cassia R, García-Rostán G et al. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 2002; 21: 7981–7990.

    CAS  PubMed  Google Scholar 

  40. Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L . P53 gene mutations are common in uterine serous carcinoma and occurs early in their pathogenesis. Am J Pathol 1997; 150: 177–185.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Sherman ME, Bur ME, Kurman RJ . P53 in endometrial cancer and its putative precursors: Evidence for diverse pathways of tumorigenesis. Human Pathol 1995; 26: 1268–1274.

    CAS  Google Scholar 

  42. Hayes MP, Ellenson LH . Molecular alterations in uterine serous carcinoma. Gynecol Oncol 2010; 116: 286–289.

    CAS  PubMed  Google Scholar 

  43. Morrison C, Zanagnolo V, Ramirez N, Cohn DE, Kelbick N, Copeland L et al. HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J Clin Oncol 2006; 24: 2376–2385.

    CAS  PubMed  Google Scholar 

  44. Tritz D, Pieretti M, Turner S, Powell D . Loss of heterozygosity in usual and special variant carcinomas of the endometrium. Hum Pathol 1997; 28: 607–612.

    CAS  PubMed  Google Scholar 

  45. Lax SF, Kendall B, Tashiro H, Slebos RJ, Hedrick L . Frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer 2000; 88: 814–824.

    CAS  PubMed  Google Scholar 

  46. Guan B, Mao TL, Panuganti PK, Kuhn E, Kurman RJ, Maeda D et al. Mutation and loss of expression of ARID1A in uterine low-grade endometrioid carcinoma. Am J Surg Pathol 2011; 35: 625–632.

    PubMed  PubMed Central  Google Scholar 

  47. Wiegand KC, Lee AF, Al-Agha OM, Chow C, Kalloger SE, Scott DW et al. Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas. J Pathol 2011; 224: 328–333.

    CAS  PubMed  Google Scholar 

  48. Risinger JI, Maxwell GL, Chandramouli GV, Jazaeri A, Aprelikova O, Patterson T et al. Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer. Cancer Res 2003; 63: 6–11.

    CAS  PubMed  Google Scholar 

  49. Bignotti E, Ravaggi A, Tassi RA, Calza S, Rossi E, Falchetti M et al. Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas. Brit J Cancer 2008; 99: 768–773.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Dainty LA, Risinger JI, Morrison C, Chandramouli GV, Bidus MA, Zahn C et al. Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma. Gynecol Oncol 2007; 105: 563–567.

    CAS  PubMed  Google Scholar 

  51. Allard JE, Risinger JI, Morrison C, Young G, Rose GS, Fowler J et al. Overexpression of folate binding protein is associated with shortened progression-free survival in uterine adenocarcinomas. Gynecol Oncol 2007; 107: 52–57.

    CAS  PubMed  Google Scholar 

  52. Moreno-Bueno G, Sánchez-Estévez C, Cassia R, Rodríguez-Perales S, Díaz-Uriarte R, Domínguez O et al. Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 2003; 63: 5697–5702.

    CAS  PubMed  Google Scholar 

  53. Maxwell GL, Chandramouli GV, Dainty L, Litzi TJ, Berchuck A, Barrett JC et al. Microarray analysis of endometrial carcinomas and mixed mullerian tumors reveals distinct gene expression profiles associated with different histologic types of uterine cancer. Clin Cancer Res 2005; 11: 4056–4066.

    CAS  PubMed  Google Scholar 

  54. Cao QJ, Belbin T, Socci N, Balan R, Prystowsky MB, Childs G et al. Distinctive gene expression profiles by cDNA microarrays in endometrioid and serous carcinomas of the endometrium. Int J Gynecol Pathol 2004; 23: 321–329.

    PubMed  Google Scholar 

  55. Shedden KA, Kshirsagar MP, Schwartz DR, Wu R, Yu H, Misek DE et al. type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas. Clin Cancer Res 2005; 11: 2123–2131.

    CAS  PubMed  Google Scholar 

  56. Chen Y, Yao Y, Zhang L, Li X, Wang Y, Zhao L et al. cDNA microarray analysis and immunohistochemistry reveal a distinct molecular phenotype in serous endometrial cancer compared to endometrioid endometrial cancer. Exp Mol Pathol 2011; 91: 373–384.

    CAS  PubMed  Google Scholar 

  57. Risinger JI, Maxwell GL, Chandramouli GV, Aprelikova O, Litzi T, Umar A et al. Gene expression profiling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling. Cancer Res 2005; 65: 5031–5037.

    CAS  PubMed  Google Scholar 

  58. Yao Y, Chen Y, Wang Y, Li X, Wang J, Shen D et al. Molecular classification of human endometrial cancer based on gene expression profiles from specialized microarrays. Int J Gynaecol Obstet 2010; 110: 125–129.

    CAS  PubMed  Google Scholar 

  59. Huvila J, Brandt A, Rojas CR, Pasanen S, Talve L, Hirsimäki P et al. Gene expression profiling of endometrial adenocarcinomas reveals increased apolipoprotein E expression in poorly differentiated tumors. Int J Gynecol Cancer 2009; 19: 1226–1231.

    PubMed  Google Scholar 

  60. Planagumà J, Díaz-Fuertes M, Gil-Moreno A, Abal M, Monge M, García A et al. A differential gene expression profile reveals overexpression of RUNX1/AML1 in invasive endometrioid carcinoma. Cancer Res 2004; 64: 8846–8853.

    PubMed  Google Scholar 

  61. Soslow RA . Endometrial carcinomas with ambiguous features. Semin Diagn Pathol 2010; 27: 261–273.

    PubMed  Google Scholar 

  62. Tafe LJ, Garg K, Chew I, Tornos C, Soslow RA . Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms. Mod Pathol 2010; 23: 781–789.

    CAS  PubMed  Google Scholar 

  63. McCluggage WG . Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas. Int J Gynecol Cancer 2002; 12: 687–690.

    CAS  PubMed  Google Scholar 

  64. Lopez-Garcia MA, Palacios J . Pathologic and molecular features of uterine carcinosarcomas. Semin Diagn Pathol 2010; 27: 274–286.

    PubMed  Google Scholar 

  65. Matias-Guiu X, Oliva E . Pathology of the endometrium. Semin Diagn Pathol 2010; 27: 197–198.

    PubMed  Google Scholar 

  66. Castilla MÁ, Moreno-Bueno G, Romero-Pérez L, De Vijver KV, Biscuola M, López-García MÁ et al. Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma. J Pathol 2011; 223: 72–80.

    CAS  PubMed  Google Scholar 

  67. Romero-Pérez L, Castilla MÁ, López-García MA, Díaz-Martín J, Biscuola M, Ramiro-Fuentes S et al. HMGA2 and epithelial-mesenchymal transition in endometrial carcinogenesis. (submitted).

  68. Blechschmidt K, Kremmer E, Hollweck R, Mylonas I, Höfler H, Kremer M et al. The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. Diagn Mol Pathol 2007; 16: 222–228.

    CAS  PubMed  Google Scholar 

  69. Montserrat N, Mozos A, Llobet D, Dolcet X, Pons C, de Herreros AG et al. Epithelial to mesenchymal transition in early stage endometrioid endometrial carcinoma. Hum Pathol 2012; 43: 632–643.

    PubMed  Google Scholar 

  70. Llaurado M, Abal M, Castellvi J, Cabrera S, Gil-Moreno A, Perez-Benavente A et al. ETV5 transcription factor is overexpressed in ovarian cancer and regulates cell adhesion in ovarian cancer cells. Int J Cancer 2011; 130: 1532–1543.

    PubMed  Google Scholar 

  71. Monge M, Colas E, Doll A, Gonzalez M, Gil-Moreno A, Planaguma J et al. ERM/ETV5 up-regulation plays a role during myometrial infiltration through matrix metalloproteinase-2 activation in endometrial cancer. Cancer Res 2007; 67: 6753–6759.

    CAS  PubMed  Google Scholar 

  72. Planaguma J, Liljestrom M, Alameda F, Butzow R, Virtanen I, Reventos J et al. Matrix metalloproteinase-2 and matrix metalloproteinase-9 codistribute with transcription factors RUNX1/AML1 and ETV5/ERM at the invasive front of endometrial and ovarian carcinoma. Hum Pathol 2011; 42: 57–67.

    CAS  PubMed  Google Scholar 

  73. Espinosa I, Carnicer MJ, Catasús L, Canet B, D′Angelo E, Zannoni GF et al. Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Am J Surg Pathol 2010; 34: 1708–1714.

    PubMed  Google Scholar 

  74. Monge M, Doll A, Colas E, Gil-Moreno A, Castellvi J, Garcia A et al. Subtractive proteomic approach to the endometrial carcinoma invasion front. J Proteome Res 2009; 8: 4676–4684.

    CAS  PubMed  Google Scholar 

  75. Pallares J, Martinez-Guitarte JL, Dolcet X, Llobet D, Rue M, Palacios J et al. Abnormalities in NF-kB family and related proteins in endometrial carcinoma. A tissue microarray study. J Pathol 2004; 13: 569–577.

    Google Scholar 

  76. Dolcet X, Llobet D, Pallares J, Rue M, Comella JX, Matias-Guiu X . FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis. Lab Invest 2005; 85: 885–894.

    CAS  PubMed  Google Scholar 

  77. Llobet D, Eritja N, Domingo M, Bergada L, Mirantes C, Santacana M et al. Dolcet KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels. Am J Pathol 2011; 178: 1529–1543.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Llobet D, Eritja N, Encinas M, Yeramian A, Pallares J, Sorolla A et al. The multikinase inhibitor sorafenib induces apoptosis and sensitizes endometrial cancer cells to TRAIL by different mechanisms. Eur J Cancer 2010; 46: 836–850.

    CAS  PubMed  Google Scholar 

  79. Llobet D, Eritja N, Encinas M, Yeramian A, Pallares J, Sorolla A et al. CK2 controls trail and Fas sensitivity by regulating flip levels in endometrial carcinoma cells. Oncogene 2008; 27: 2513–2524.

    CAS  PubMed  Google Scholar 

  80. Pallares J, Llobet D, Santacana M, Eritja N, Velasco A, Cuevas D et al. CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation. Am J Pathol 2009; 174: 287–296.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Dolcet X, Llobet D, Encinas M, Pallares J, Cabero A, Schoenenberger JA et al. Proteasome inhibitors induce death but activate NF-KB on endometrial carcinoma cell lines and primary culture explants. J Biol Chem 2006; 281: 22118–22130.

    CAS  PubMed  Google Scholar 

  82. Pijnenborg JM, Romano A, Dam-de Veen GC, Dunselman GA, Fischer DC, Groothuis PG et al. Aberrations in the progesterone receptor gene and the risk of recurrent endometrial carcinoma. J Pathol 2005; 205: 597–605.

    CAS  PubMed  Google Scholar 

  83. Pijnenborg JM, Dam-de Veen GC, de Haan J, van Engeland M, Groothuis PG . Defective mismatch repair and the development of recurrent endometrial carcinoma. Gynecol Oncol 2004; 94: 550–559.

    CAS  PubMed  Google Scholar 

  84. Pijnenborg JM, van de Broek L, Dam de Veen GC, Roemen GM, de Haan J, van Engeland M et al. TP53 overexpression in recurrent endometrial carcinoma. Gynecol Oncol 2006; 100: 397–404.

    CAS  PubMed  Google Scholar 

  85. Pijnenborg JM, Kisters N, van Engeland M, Dunselman GA, de Haan J, de Goeij AF et al. APC, beta-catenin, and E-cadherin and the development of recurrent endometrial carcinoma. Int J Gynecol Cancer 2004; 14: 947–956.

    CAS  PubMed  Google Scholar 

  86. Santacana M, Yeramian A, Velasco A, Bergada L, García V, Azueta A et al. Immunohistochemical features of post-radiation vaginal recurrences of endometrioid carcinomas of the endometrium. Role for proteins involved in resistance to apoptosis and hypoxia. Histopathology 2012; 60: 460–471.

    PubMed  Google Scholar 

  87. Yeramian A, Santacana M, Sorolla A, Llobet D, Encinas M, Velasco A et al. Nuclear factor beta /p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1alpha in an independent manner. Lab Invest 2011; 91: 859–871.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from FIS PI100922, Fundación Mutua Madrileña AP75732010, FIS PI080410, 2009SGR794, RD06/0020/1034, RD06/0020/0013, RD06/0020/0058, RD06/0020/0015, Fundación Asociación Española contra el Cancer and programa de intensificación de la investigación, Instituto Carlos III. AY holds a postdoctoral fellowship from Programa Juan de la Cierva, Ministerio de Ciencia e Innovación (JCI-2008-1969).

Author information

Authors and Affiliations

  1. Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain

    A Yeramian, X Dolcet & X Matias-Guiu

  2. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas ‘Alberto Sols’, CSIC-UAM, IdiPAZ (Instituto de Investigación Sanitaria La Paz), and Fundación MD Anderson Cancer Centre, Madrid, Spain

    G Moreno-Bueno

  3. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Institut d′Investigació Biomèdica (IBB) SantPau, Autonomous University of Barcelona, Barcelona, Spain

    L Catasus & J Prat

  4. Oncologic Research Laboratory, Complejo Hospitalario de Santiago de Compostela, Santiago de Compostela, Spain

    M Abal

  5. Biomedical Research Unit, Vall d’Hebron Research Institute and University Hospital, Barcelona, Spain

    E Colas & J Reventos

  6. Department of Pathology, Hospital Universitario Virgen del Rocío and Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain

    J Palacios

Authors
  1. A Yeramian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Moreno-Bueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. X Dolcet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Catasus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Abal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Colas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Reventos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Palacios
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Prat
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. X Matias-Guiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X Matias-Guiu.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yeramian, A., Moreno-Bueno, G., Dolcet, X. et al. Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene 32, 403–413 (2013). https://doi.org/10.1038/onc.2012.76

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2012.76

Keywords

This article is cited by

Search

Advanced search

Quick links