Familial Cancer

, Volume 9, Issue 3, pp 383–387 | Cite as

High risk for neoplastic transformation of endometriosis in a carrier of lynch syndrome

  • Christine Nyiraneza
  • Etienne Marbaix
  • Mireille Smets
  • Christine Galant
  • Christine Sempoux
  • Karin Dahan


Lynch syndrome is an autosomal dominant cancer-susceptibility disorder caused by mutations in DNA mismatch repair genes. Women with Lynch syndrome have an increased lifetime risk for endometrial and ovarian cancers. While there is evidence of efficacy for prophylactic surgery, no standard recommendations have been developed to support screening for premalignant endometrial and ovarian epithelial lesions in high-risk women. Here, we report a case of a healthy woman carrying a germline mutation in MLH1 gene with endometrial intra-epithelial neoplasia and ovarian endometriotic lesions exhibiting a loss of MLH1 protein expression. This case report illustrates the malignant potential of endometriosis, and highlights the need for a meticulous management of gynecologic premalignant precursor lesions in reducing cancer risk among related Lynch syndrome women.


Lynch syndrome MMR deficiency Endometrial cancer Ovarian cancer Endometriosis Genetic counseling Cancer prevention 



Hereditary non-polyposis colorectal cancer


DNA mismatch repair system


Microsatellite instability


  1. 1.
    Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932CrossRefPubMedGoogle Scholar
  2. 2.
    Schmeler KM, Lynch HT, Chen LM et al (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354:261–269CrossRefPubMedGoogle Scholar
  3. 3.
    Seiden MV, Patel D, O’Neill MJ, Oliva E (2007) Case records of the Massachusetts General Hospital. Case 13–2007. A 46-year-old woman with gynecologic and intestinal cancers. N Engl J Med 356:1760–1769CrossRefPubMedGoogle Scholar
  4. 4.
    Boland CR, Thibodeau SN, Hamilton SR et al (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMedGoogle Scholar
  5. 5.
    Wang Q, Desseigne F, Lasset C et al (1997) Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families. Int J Cancer 73:831–836CrossRefPubMedGoogle Scholar
  6. 6.
    Lindor NM, Petersen GM, Hadley DW et al (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296:1507–1517CrossRefPubMedGoogle Scholar
  7. 7.
    Mutter GL, Baak JP, Crum CP, Richart RM, Ferenczy A, Faquin WC (2000) Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol 190:462–469CrossRefPubMedGoogle Scholar
  8. 8.
    Esteller M, Catasus L, Matias-Guiu X et al (1999) hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 155:1767–1772PubMedGoogle Scholar
  9. 9.
    Simpkins SB, Bocker T, Swisher EM et al (1999) MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers. Hum Mol Genet 8:661–666CrossRefPubMedGoogle Scholar
  10. 10.
    Knudson AG (1996) Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol 122:135–140CrossRefPubMedGoogle Scholar
  11. 11.
    Kinzler KW, Vogelstein B (1997) Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 386:761–763CrossRefPubMedGoogle Scholar
  12. 12.
    Rahner N, Friedrichs N, Steinke V et al (2008) Coexisting somatic promoter hypermethylation and pathogenic MLH1 germline mutation in Lynch syndrome. J Pathol 214:10–16CrossRefPubMedGoogle Scholar
  13. 13.
    Ollikainen M, Hannelius U, Lindgren CM et al (2007) Mechanisms of inactivation of MLH1 in hereditary nonpolyposis colorectal carcinoma: a novel approach. Oncogene 26:4541–4549CrossRefPubMedGoogle Scholar
  14. 14.
    Hemminki K, Aaltonen L, Li X (2003) Subsequent primary malignancies after endometrial carcinoma and ovarian carcinoma. Cancer 97:2432–2439CrossRefPubMedGoogle Scholar
  15. 15.
    Lynch HT, de la Chapelle A (1999) Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 36:801–818PubMedGoogle Scholar
  16. 16.
    Watson P, Bützow R, Lynch HT et al (2001) The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 82:223–228CrossRefPubMedGoogle Scholar
  17. 17.
    Varma R, Rollason T, Gupta JK, Maher ER (2004) Endometriosis and the neoplastic process. Reproduction 127:293–304CrossRefPubMedGoogle Scholar
  18. 18.
    Martini M, Ciccarone M, Garganese G et al (2002) Possible involvement of hMLH1, p16(INK4a) and PTEN in the malignant transformation of endometriosis. Int J Cancer 102:398–406CrossRefPubMedGoogle Scholar
  19. 19.
    Prowse AH, Manek S, Varma R et al (2006) Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer 119:556–562CrossRefPubMedGoogle Scholar
  20. 20.
    Nezhat F, Datta MS, Hanson V et al (2008) The relationship of endometriosis and ovarian malignancy: a review. Fertil Steril 90:1559–1570CrossRefPubMedGoogle Scholar
  21. 21.
    Ballweg ML (2004) Impact of endometriosis on women’s health: comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol 18:201–218CrossRefPubMedGoogle Scholar
  22. 22.
    Matsuo K, Alonsozana EL, Eno ML, Rosenshein NB, Im DD (2009) Primary peritoneal clear cell adenocarcinoma arising in previous abdominal scar for endometriosis surgery. Arch Gynecol Obstet 280:637–641CrossRefPubMedGoogle Scholar
  23. 23.
    Dove-Edwin I, Boks D, Goff S et al (2002) The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 94:1708–1712CrossRefPubMedGoogle Scholar
  24. 24.
    Järvinen HJ, Renkonen-Sinisalo L, Aktán-Collán K, Peltomäki P, Aaltonen LA, Mecklin JP (2009) Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol 27:4793–4797CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Christine Nyiraneza
    • 1
  • Etienne Marbaix
    • 2
  • Mireille Smets
    • 3
  • Christine Galant
    • 2
  • Christine Sempoux
    • 2
  • Karin Dahan
    • 1
    • 4
  1. 1.Center for Human Genetics, Cliniques universitaires Saint-LucUniversité catholique de LouvainBrusselsBelgium
  2. 2.Department of Pathology, Cliniques universitaires Saint-LucUniversité catholique de LouvainBrusselsBelgium
  3. 3.Department of Gynecology, Cliniques universitaires Saint-LucUniversité catholique de LouvainBrusselsBelgium
  4. 4.Center for Human GeneticsInstitute of Pathology and GeneticsGosseliesBelgium

Personalised recommendations