Skip to main content
SpringerLink
Log in

Vorläuferläsionen des Endometriumkarzinoms

Diagnostik und Molekularpathologie

Precursor lesions of endometrial carcinoma

Diagnostic approach and molecular pathology

  • Hauptreferate
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Für Endometriumkarzinome sind 2 Vorläuferläsionen bekannt: Die häufigen endometrioiden Adenokarzinome (Typ-1-Karzinome) entwickeln sich aus einer atypischen Endometriumhyperplasie, seröse und z. T. klarzellige Karzinome (Typ-2-Karzinome) aus einem intraepithelialen Karzinom („endometrial intraepithelial carcinoma“, EIC). An der atypischen Hyperplasie, die ein Progressionspotenzial von bis zu 40% aufweist, wird eine schlechte Reproduzierbarkeit kritisiert. Eine bessere Reproduzierbarkeit bietet das Konzept der „endometrial intraepithelial neoplasia“ (EIN), dessen Kategorien aber nicht exakt mit jenen der World-Health-Organization(WHO)-Klassifikation der Endometriumhyperplasie übereinstimmen. Die EIN umfassen den Großteil der atypischen Hyperplasien, aber auch etwa die Hälfte der komplexen Hyperplasien ohne Atypien. Selten kann die atypische Hyperplasie mit einem sekretorischen oder muzinösen Zelltyp assoziiert sein, mögliche Vorläufer der sekretorischen bzw. muzinösen Karzinome. Durch eine lang dauernde, hochdosierte Gestagentherapie bilden sich bis zu zwei Drittel der atypischen Hyperplasien vollständig zurück. Immunhistochemisch unterscheiden sich atypische Hyperplasie bzw. EIN durch häufige PTEN bzw. Pax-2-Negativität vom EIC mit seiner hochgradigen p53-Reaktivität und hohem Ki67-Färbeindex.

Abstract

For endometrial adenocarcinoma two precursor lesions are known: endometrioid adenocarcinoma which is the most frequent type 1 carcinoma develops from atypical endometrial hyperplasia whereas endometrial intraepithelial carcinoma (EIC) is the precursor of serous carcinoma and a subset of clear cell carcinoma both representing type 2 carcinomas. Atypical hyperplasia which shows progression rates into carcinoma of up to 40% is challenged by its poor interobserver reproducibility. A better reproducibility is obtained by the endometrial intraepithelial neoplasia (EIN) concept with fewer categories but it is not compatible with the World Health Organization (WHO) classification of endometrial hyperplasia. The EIN concept includes not only the vast majority of the WHO atypical hyperplasia but also approximately half of the complex hyperplasia without atypia. Rarely, atypical hyperplasia is associated with a secretory or mucinous cell type and two thirds of atypical hyperplasia resolve under long-term high dosage progestin therapy. Immunohistochemistry aids in the differential diagnosis of atypical hyperplasia and EIC. Atypical hyperplasia/EIN frequently show PTEN and/or Pax-2 negativity and low Ki-67 and differ from EIC which shows strong diffuse p53 staining and high Ki-67 staining index.

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

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5

Abbreviations

EIC:

intraepitheliales Karzinom des Endometriums („endometrial intraepithelial carcinoma“)

EIN:

intraepitheliale Neoplasie des Endometriums („endometrial intraepithelial neoplasia“)

Literatur

  1. Ambros RA (2000) Simple hyperplasia of the endometrium: an evaluation of proliferative activity by Ki-67 immunostaining. Int J Gynecol Pathol 19:206–211

    Article  PubMed  CAS  Google Scholar 

  2. Ambros RA, Sherman ME, Zahn CM et al (1995) Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation. Hum Pathol 26:1260–1267

    Article  PubMed  CAS  Google Scholar 

  3. Baak JP, Mutter GL, Robboy S et al (2005) The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer 103:2304–2312

    Article  PubMed  CAS  Google Scholar 

  4. Baak JP, Orbo A, Van Diest PJ et al (2001) Prospective multicenter evaluation of the morphometric D-score for prediction of the outcome of endometrial hyperplasias. Am J Surg Pathol 25:930–935

    Article  PubMed  CAS  Google Scholar 

  5. Baak JP, Van Diermen B, Steinbakk A et al (2005) Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression. Hum Pathol 36:555–561

    Article  PubMed  CAS  Google Scholar 

  6. Bergeron C, Nogales FF, Masseroli M et al (1999) A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens. Am J Surg Pathol 23:1102–1108

    Article  PubMed  CAS  Google Scholar 

  7. Chiesa-Vottero AG, Malpica A, Deavers MT et al (2007) Immunohistochemical overexpression of p16 and p53 in uterine serous carcinoma and ovarian high-grade serous carcinoma. Int J Gynecol Pathol 26:328–333

    Article  PubMed  Google Scholar 

  8. Dallenbach-Hellweg G (1987) Histopathology of the endometrium. Springer, Berlin Heidelberg New York

  9. Ellenson LH, Ronnett BM, Kurman RJ (2011) Precursor lesion of endometrial carcinoma. In: Kurman RJ, Ellenson LH, Ronnett BM (Hrsg) Blaustein’s pathology of the female genital tract. Springer, Berlin Heidelberg New York Tokio, S 360–391

  10. Hecht JL, Ince TA, Baak JP et al (2005) Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis. Mod Pathol 18:324–330

    Article  PubMed  Google Scholar 

  11. Jarboe EA, Pizer ES, Miron A et al (2009) Evidence for a latent precursor (p53 signature) that may precede serous endometrial intraepithelial carcinoma. Mod Pathol 22:345–350

    Article  PubMed  CAS  Google Scholar 

  12. Kendall BS, Ronnett BM, Isacson C et al (1998) Reproducibility of the diagnosis of endometrial hyperplasia, atypical hyperplasia, and well-differentiated carcinoma. Am J Surg Pathol 22:1012–1019

    Article  PubMed  CAS  Google Scholar 

  13. Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia. A long-term study of „untreated“ hyperplasia in 170 patients. Cancer 56:403–412

    Article  PubMed  CAS  Google Scholar 

  14. Lacey JV Jr, Mutter GL, Nucci MR et al (2008) Risk of subsequent endometrial carcinoma associated with endometrial intraepithelial neoplasia classification of endometrial biopsies. Cancer 113:2073–2081

    Article  PubMed  Google Scholar 

  15. Lax SF (2007) Molecular genetic changes in epithelial, stromal and mixed neoplasms of the endometrium. Pathology 39:46–54

    Article  PubMed  CAS  Google Scholar 

  16. Lax SF (2004) Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 444:213–223

    Article  PubMed  CAS  Google Scholar 

  17. Lax SF, Pizer ES, Ronnett BM et al (1998) Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum Pathol 29:551–558

    Article  PubMed  CAS  Google Scholar 

  18. Matias-Guiu X, Catasus L, Bussaglia E et al (2001) Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 32:569–577

    Article  PubMed  CAS  Google Scholar 

  19. Monte NM, Webster KA, Neuberg D et al (2010) Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Cancer Res 70:6225–6232

    Article  PubMed  CAS  Google Scholar 

  20. Mutter GL (2000) Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group. Gynecol Oncol 76:287–290

    Article  PubMed  CAS  Google Scholar 

  21. Mutter GL (2000) Histopathology of genetically defined endometrial precancers. Int J Gynecol Pathol 19:301–309

    Article  PubMed  CAS  Google Scholar 

  22. Mutter GL, Baak JP, Crum CP et al (2000) Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol 190:462–469

    Article  PubMed  CAS  Google Scholar 

  23. Park H, Seok JM, Yoon BS et al (2011) Effectiveness of high-dose progestin and long-term outcomes in young women with early-stage, well-differentiated endometrioid adenocarcinoma of uterine endometrium. Arch Gynecol Obstet.; doi 10.1007/s00404-011-1959-x

  24. Randall TC, Kurman RJ (1997) Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 90:434–440

    Article  PubMed  CAS  Google Scholar 

  25. Reed SD, Voigt LF, Newton KM et al (2009) Progestin therapy of complex endometrial hyperplasia with and without atypia. Obstet Gynecol 113:655–662

    PubMed  CAS  Google Scholar 

  26. Santin AD, Bellone S, Van Stedum S et al (2005) Determination of HER2/neu status in uterine serous papillary carcinoma: comparative analysis of immunohistochemistry and fluorescence in situ hybridization. Gynecol Oncol 98:24–30

    Article  PubMed  CAS  Google Scholar 

  27. Sherman ME, Ronnett BM, Ioffe OB et al (2008) Reproducibility of biopsy diagnoses of endometrial hyperplasia: evidence supporting a simplified classification. Int J Gynecol Pathol 27:318–325

    Article  PubMed  Google Scholar 

  28. Sherman ME, Sturgeon S, Brinton LA et al (1997) Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas. Mod Pathol 10:963–968

    PubMed  CAS  Google Scholar 

  29. Tashiro H, Isacson C, Levine R et al (1997) p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol 150:177–185

    PubMed  CAS  Google Scholar 

  30. Tavassoli FA, Devilee P (Hrsg) (2003) Tumours of the breast and female genital organs. IARC, Lyon

  31. Trimble CL, Kauderer J, Zaino R et al (2006) Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 106:812–819

    Article  PubMed  Google Scholar 

  32. Wheeler DT, Bell KA, Kurman RJ et al (2000) Minimal uterine serous carcinoma: diagnosis and clinicopathologic correlation. Am J Surg Pathol 24:797–806

    Article  PubMed  CAS  Google Scholar 

  33. Wheeler DT, Bristow RE, Kurman RJ (2007) Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Am J Surg Pathol 31:988–998

    Article  PubMed  Google Scholar 

  34. Yemelyanova A, Ji H, Shih Ie M et al (2009) Utility of p16 expression for distinction of uterine serous carcinomas from endometrial endometrioid and endocervical adenocarcinomas: immunohistochemical analysis of 201 cases. Am J Surg Pathol 33:1504–1514

    Article  PubMed  Google Scholar 

  35. Yin Y, Shen WH (2008) PTEN: a new guardian of the genome. Oncogene 27:5443–5453

    Article  PubMed  CAS  Google Scholar 

  36. Zaino RJ, Kauderer J, Trimble CL et al (2006) Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 106:804–811

    Article  PubMed  Google Scholar 

  37. Zheng W, Liang SX, Yu H et al (2004) Endometrial glandular dysplasia: a newly defined precursor lesion of uterine papillary serous carcinoma. Part I: morphologic features. Int J Surg Pathol 12:207–223

    Article  PubMed  Google Scholar 

  38. Zheng W, Xiang L, Fadare O et al (2011) A proposed model for endometrial serous carcinogenesis. Am J Surg Pathol 35:e1–e14

    Article  PubMed  Google Scholar 

  39. Zielonke N, Hackl M, Baldaszti E (2010) Krebsinzidenz und Krebsmortalität in Österreich. Statistik Austria, Wien

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Institut für Pathologie, LKH Graz West, Göstingerstr. 22, 8020, Graz, Österreich

    S. Lax

Authors
  1. S. Lax
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Lax.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lax, S. Vorläuferläsionen des Endometriumkarzinoms. Pathologe 32 (Suppl 2), 255 (2011). https://doi.org/10.1007/s00292-011-1514-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s00292-011-1514-3

Schlüsselwörter

Keywords

Search

Navigation