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Uterine Cancer pp 25–32Cite as

Hereditary Cancers of the Endometrium: HNPCC Syndrome and Beyond

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Abstract

The incidence of endometrial cancer is increasing worldwide [1]. Identifying women who are at increased risk of endometrial cancer can help in the early diagnosis and prevention of the disease. Obesity, early menarche and late menopause, tamoxifen use, hereditary factors like hereditary nonpolyposis colorectal carcinoma (HNPCC) syndrome, diabetes mellitus, systemic hypertension, etc. are some of the high-risk factors associated with carcinoma of the endometrium. The lifetime risk for endometrial cancer increases from 2.6 % to about 60 % in HNPCC syndrome [2].

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29. 2.

    Article  PubMed  Google Scholar 

  2. Torres ML, Weaver AL, Kumar S, Uccella S, Famuyide AO, Cliby WA, et al. Risk factors for developing endometrial cancer after benign endometrial sampling. Obstet Gynecol. 2012;120(5):998–1004.

    PubMed Central  PubMed  Google Scholar 

  3. Folkins AK, Longacre TA. Hereditary gynaecological malignancies: advances in screening and treatment. Histopathology. 2013;62:2–30.

    Article  PubMed  Google Scholar 

  4. Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81:214–8.

    Article  CAS  PubMed  Google Scholar 

  5. Lu KH, Dinh M, Kohlmann W, et al. Gynecologic cancer as a ‘sentinel cancer’ for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol. 2005;105:569–74.

    Article  PubMed  Google Scholar 

  6. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116:1453–6.

    Article  CAS  PubMed  Google Scholar 

  7. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and micro- satellite instability. J Natl Cancer Inst. 2004;96:261–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Steinke V, Engel C, Büttner R, Schackert HK, Schmiegel WH, Propping P. Hereditary Nonpolyposis Colorectal Cancer (HNPCC)/Lynch syndrome. 2013. doi:10.3238/arztebl.2013.0032

  9. Lancaster JM, Powell CB, Kauff ND, et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2007;107:159–62. 136.

    Article  PubMed  Google Scholar 

  10. Hampel H, Frankel W, Panescu J, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006;66:7810–7.

    Article  CAS  PubMed  Google Scholar 

  11. Mills AM, Liou S, Ford JM, Berek JS, Pai RK, Longacre TA. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Mod Pathol. 2011;24:260A.

    Google Scholar 

  12. Ryan P, Mulligan AM, Aronson M, et al. Comparison of clinical schemas and morphologic features in predicting Lynch syndrome in mutation-positive patients with endometrial cancer encountered in the context of familial gastrointestinal cancer registries. Cancer. 2012;118:681–8.

    Article  PubMed  Google Scholar 

  13. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1–18. 11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Wang Y, Li J, Cragun J. Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium. J Hematol Oncol. 2013;6(1):1. doi:10.1186/1756-8722-6-22.

    Article  Google Scholar 

  15. Garg K, Shih K, Barakat R, Zhou Q, Iasonos A, Soslow RA. Endometrial carcinomas in women aged 40 years and younger: tumours associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset. Am J Surg Pathol. 2009;33:1869–77.

    Article  PubMed  Google Scholar 

  16. Peltomaki P, Lothe RA, Aaltonen LA, et al. Microsatellite instability is associated with tumours that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res. 1993;53:5853–5.

    CAS  PubMed  Google Scholar 

  17. Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003;21:1174–9.

    Article  CAS  PubMed  Google Scholar 

  18. Gurin CC, Federici MG, Kang L, Boyd J. Causes and consequences of microsatellite instability in endometrial carcinoma. Cancer Res. 1999;59:462–6. 118.

    CAS  PubMed  Google Scholar 

  19. Bonadona V, Bonaiti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305:2304–10.

    Article  CAS  PubMed  Google Scholar 

  20. Senter L, Clendenning M, Sotamaa K, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008;135:419–28.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Offman SL, Liou S, Mills AM, Longacre TA. A clinicopathologic analysis of 419 consecutive endometrial carcinomas with emphasis on lower uterine segment tumours. Mod Pathol. 2012;25:290A–1.

    Google Scholar 

  22. Broaddus RR, Lynch HT, Chen LM, et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer. 2006;106:87–94.

    Article  CAS  PubMed  Google Scholar 

  23. South SA, Hutton M, Farrell C, Mhawech-Fauceglia P, Rodabaugh KJ. Uterine carcinosarcoma associated with hereditary nonpolyposis colorectal cancer. Obstet Gynecol. 2007;110:543–5.

    Article  PubMed  Google Scholar 

  24. Honoré LH, Hanson J, Andrew SE. Microsatellite instability in endometrioid endometrial carcinoma: correlation with clinically relevant pathologic variables. Int J Gynecol Cancer. 2006;16(3):1386–92.

    Article  PubMed  Google Scholar 

  25. Altrabulsi B, Malpica A, Deavers MT, Bodurka DC, Broaddus R, Silva EG. Undifferentiated carcinoma of the endometrium. Am J Surg Pathol. 2005;29:1316–21.

    Article  PubMed  Google Scholar 

  26. Silva EG, Deavers MT, Bodurka DC, Malpica A. Association of low-grade endometrioid carcinoma of the uterus and ovary with undifferentiated carcinoma: a new type of dedifferentiated carcinoma? Int J Gynecol Pathol. 2006;25:52–8.

    Article  PubMed  Google Scholar 

  27. Garg K, Leitao Jr MM, Kauff ND, et al. Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumour morphology enhances detection of mismatch repair abnormalities. Am J Surg Pathol. 2009;33:925–33.

    Article  PubMed  Google Scholar 

  28. Shia JS, Black DB, Hummer AJ, et al. Routinely assessed morphologic features correlate with microsatellite instability status in endometrial cancer. Hum Pathol. 2008;39:116–25. 23.

    Article  CAS  PubMed  Google Scholar 

  29. Jensen KC, Mariappan MR, Putcha GV, et al. Microsatellite instability and mismatch repair protein defects in ovarian epithelial neoplasms in patients 50 years of age and younger. Am J Surg Pathol. 2008;32:1029–37.

    Article  PubMed  Google Scholar 

  30. Ollikainen M, Abdel-Rahman WM, Moisio AL, et al. Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or separate syndrome? J Clin Oncol. 2005;23:4609–16.

    Article  CAS  PubMed  Google Scholar 

  31. Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352:1851–60.

    Article  CAS  PubMed  Google Scholar 

  32. Lu KH, Schorge JO, Rodabaugh KJ, et al. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. J Clin Oncol. 2007;25:5158–64.

    Article  CAS  PubMed  Google Scholar 

  33. Wagner A, Hendriks Y, Meijers-Heijboer EJ, et al. Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree. J Med Genet. 2001;38:318–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Kwon JS, Scott JL, Gilks CB, Daniels MS, Sun CC, Lu KH. Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncol. 2011;29:2247–52. 128.

    Article  PubMed  Google Scholar 

  35. Modica I, Soslow RA, Black D, Tornos C, Kauff N, Shia J. Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma. Am J Surg Pathol. 2007;31:744–51.

    Article  PubMed  Google Scholar 

  36. Boland CR, Thibodeau SN, Hamilton SR, et al. 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. 1998;58:5248–57.

    CAS  PubMed  Google Scholar 

  37. Vasen HF, Moslein G, Alonso A, Bernstein I, Bertario L, Blanco I, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet. 2007;44:353–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. The National Comprehensive Cancer Network guidelines. Available at: http://www.nccn.org. Retrieved 14 Dec 2013.

  39. Dove-Edwin I, Boks D, Goff S, et al. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal cancer. Cancer. 2002;94:1708Y1712. 10.

    Article  Google Scholar 

  40. Renkonen-Sinisalo L, Bützow R, Leminen A, Lehtovirta P, Mecklin JP, Järvinen HJ. Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome. Int J Cancer. 2007;120:821–4.

    Article  CAS  PubMed  Google Scholar 

  41. Lécuru F, Huchon C, Metzger U, Bats AS, Le Frère Belda MA, Olschwang S, Puig PL. Contribution of ultrasonography to endometrial cancer screening in patients with hereditary nonpolyposis colorectal cancer/Lynch syndrome. Int J Gynecol Cancer. 2010;20(4):583–7.

    Article  PubMed  Google Scholar 

  42. Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354:261–9.

    Article  CAS  PubMed  Google Scholar 

  43. Yang KY, Caughey AB, Little SE, Cheung MK, Chen LM. A cost-effectiveness analysis of prophylactic surgery versus gynecologic surveillance for women from hereditary non-polyposis colorectal cancer (HNPCC) families. Fam Cancer. 2011;10:535–43.

    Article  PubMed  Google Scholar 

  44. Lavie O, Ben-Arie A, Segev Y, et al. BRCA germline mutations in women with uterine serous carcinoma – still a debate. Int J Gynecol Cancer. 2010;20(9):1531–4.

    PubMed  Google Scholar 

  45. Bruchim I, Amichay K, Kidron D, Attias Z, Biron-Shental T, Drucker L, et al. BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma. Int J Gynecol Cancer. 2010;20(7):1148–53.

    Article  PubMed  Google Scholar 

  46. Kwon JS, Lenehan J, Carey M, et al. Prolonged survival among women with BRCA germline mutations and advanced endometrial cancer: a case series. Int J Gynecol Cancer. 2008;18:546Y549.

    Google Scholar 

  47. Schmeler KM, Daniels MS, Brandt AC, Lu KH. Endometrial cancer in an adolescent: A possible manifestation of Cowden Syndrome. Obstet Gynecol. 2009;114(2):477–9.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Gynecological Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwavidyapeetham, Kochi, India

    Anupama Rajanbabu MD, MRCOG

  2. Division of Surgical and Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada

    Walter H. Gotlieb MD, PhD

Authors
  1. Anupama Rajanbabu MD, MRCOG
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  2. Walter H. Gotlieb MD, PhD
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Corresponding author

Correspondence to Anupama Rajanbabu MD, MRCOG .

Editor information

Editors and Affiliations

  1. Obstetrics and Gynecology, University College of Medical Sciences, New Delhi, India

    Shalini Rajaram

  2. Surgical &Gynec Oncology, Lakeshore & Welcare Hospitals, Kochi, Kerala, India

    Chitrathara K

  3. Gynec Onclogy, Tata Memorial Hospital, Mumbai, India

    Amita Maheshwari

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© 2015 Springer India

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Rajanbabu, A., Gotlieb, W.H. (2015). Hereditary Cancers of the Endometrium: HNPCC Syndrome and Beyond. In: Rajaram, S., K, C., Maheshwari, A. (eds) Uterine Cancer. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1892-0_3

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  • DOI: https://doi.org/10.1007/978-81-322-1892-0_3

  • Publisher Name: Springer, New Delhi

  • Print ISBN: 978-81-322-1891-3

  • Online ISBN: 978-81-322-1892-0

  • eBook Packages: MedicineMedicine (R0)

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