- •In this systematic review 747 ovarian cancers in women with LS were evaluated.
- •The mean age of diagnosis of ovarian cancer was 45.3 years (range 19–82 years).
- •Most common histological types were endometrioid or clear cell carcinomas.
- •65% of ovarian cancers were early stage (FIGO I/II) with a good overall survival.
- •In six studies, 7/22 (32%) ovarian cancers were found during surveillance.
The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS.
All studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were evaluated. Two reviewers independently evaluated eligible studies and extracted data on age at diagnosis, histological type, FIGO stage, and way of detection according to pre-specified criteria. The studies were assessed for quality using the Newcastle-Ottawa quality assessment scales.
The quality score of the 49 identified studies was at least 6 out of 8 and provide clinical information on 747 LS women with ovarian cancer. The mean age at diagnosis was 45.3 (range 19–82) years. Most frequent mutations were MSH2 (47%) and MLH1 (38%). Histopathological data were available for 445 women. The most frequently reported histological type was mixed type (mucinous/endometrioid/clear cell carcinomas) (n = 136; 31%). Most tumours (281, 65%) were diagnosed at an early stage (FIGO I/II). Six studies evaluating the effect of surveillance of ovarian cancer, reported that seven of 22 (32%) ovarian cancers were found during surveillance, 6/7 (86%) were detected at an early stage.
This systematic review describes that ovarian cancer in women with LS has a wide age-range of onset, is often diagnosed at an early stage with frequently endometrioid/clear cell histology. Data about the role of surveillance in detection of ovarian cancer in women with LS are scarce however detection at an early stage seems possible.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to European Journal of Cancer
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Molecular genetics of hereditary ovarian cancer.Oncology. 1998; 12 (discussion 409–10, 413): 399-406
- The extracolonic cancer spectrum in females with the common ‘South African’ hMLH1 c.C1528T mutation.Fam Cancer. 2008; 7: 191-198https://doi.org/10.1007/s10689-007-9174-4
- Microsatellite instability differences between familial and sporadic ovarian cancers.Carcinogenesis. 1996; 17: 1799-1804https://doi.org/10.1093/carcin/17.9.1799
- Hereditary colorectal cancer.N Engl J Med. 2003; 348: 919-932https://doi.org/10.1056/NEJMra012242v
- The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.Gastroenterology. 2008; 135: 419-428https://doi.org/10.1053/j.gastro.2008.04.026
- Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations.Clin Genet. 2009; 75: 141-149https://doi.org/10.1111/j.1399-0004.2008.01125.x
- Cancer risk in mutation carriers of DNA-mismatch-repair genes.Int J Cancer. 1999; 81: 214-218https://doi.org/10.1002/(SICI)1097-0215(19990412)
- Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families.Acta Obstet Gynecol Scand. 2008; 87: 1129-1135https://doi.org/10.1080/00016340802443806
- Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis.Gastroenterology. 1996; 110: 1020-1027https://doi.org/10.1053/gast.1996.v110.pm8612988
- Cancer risk associated with germline DNA mismatch repair gene mutations.Hum Mol Genet. 1997; 6: 105-110https://doi.org/10.1093/hmg/6.1.105
- Risks of Lynch syndrome cancers for MSH6 mutation carriers.J Natl Cancer Inst. 2010; 102: 193-201
- Cumulative incidence of colorectal and extracolonic cancers in MLH1 and MSH2 mutation carriers of hereditary nonpolyposis colorectal cancer.J Gastrointest Surg. 1998; 2: 67-71https://doi.org/10.1016/S1091-255X(98)80105-4
- MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.J Clin Oncol. 2001; 19: 4074-4080
- Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance.Gastroenterology. 2004; 27: 17-25https://doi.org/10.1053/j.gastro.2004.03.068
- Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset.Gastroenterology. 2005; 129: 415-421https://doi.org/10.1053/j.gastro.2005.05.011
- Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainment.J Med Genet. 2005; 42: 491-496https://doi.org/10.1136/jmg.2004.024299
- The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome.Int J Cancer. 2008; 123: 444-449https://doi.org/10.1002/ijc.23508
- Cancer risk in young women at risk of hereditary nonpolyposis colorectal cancer: implications for gynecologic surveillance.Gynecol Oncol. 2001; 80: 346-349https://doi.org/10.1006/gyno.2000.6065
- Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome.Int J Cancer. 2006; 120: 821-824https://doi.org/10.1002/ijc.22446
- Improvement of endometrial biopsy over transvaginal ultrasound alone for endometrial surveillance in women with Lynch syndrome.Fam Cancer. 2009; 8: 391-397https://doi.org/10.1007/s10689-009-9252-x
- The additional value of endometrial sampling in the early detection of endometrial cancer in women with Lynch syndrome.Gynecol Oncol. 2013 Nov; 131: 304-308https://doi.org/10.1016/j.ygyno.2013.05.032
- Impact of gynecological screening in Lynch syndrome carriers with an MSH2 mutation.Clin Genet. 2013 Apr; 83: 359-364https://doi.org/10.1111/j.1399-0004.2012.01929.x
- Screening for ovarian cancer: a pilot randomised controlled trial.Lancet. 1999; 353: 1207-1210https://doi.org/10.1016/S0140-6736(98)10261-1
- Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).Lancet Oncol. 2009 Apr; 10: 327-340https://doi.org/10.1016/S1470-2045(09)70026-9
- Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule.J Clin Oncol. 2013; 31: 49-57https://doi.org/10.1200/JCO.2011.39.7638
- No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study.Br J Cancer. 2007; 96: 1335-1342https://doi.org/10.1038/sj.bjc.6603725
- Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial.JAMA. 2011; 305: 2295-2303https://doi.org/10.1001/jama.2011.766
- Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?.Int J Cancer. 2009; 124: 919-923https://doi.org/10.1002/ijc.24038
- Survival of patients with ovarian cancer due to a mismatch repair defect.Fam Cancer. 2005; 4: 301-305https://doi.org/10.1007/s10689-005-6573-2
- High risk of endometrial cancer in colorectal cancer kindred is pathognomonic for MMR-mutation carriers.Fam Cancer. 2009; 8: 145-151https://doi.org/10.1007/s10689-008-9219-3
- Ovarian endometrioid adenocarcinoma: incidence and clinical significance of the morphologic and immunohistochemical markers of mismatch repair protein defects and tumor microsatellite instability.Am J Surg Pathol. 2012; 36: 163-172https://doi.org/10.1097/PAS.0b013e31823bc434
- Distinct molecular profiles in Lynch syndrome-associated and sporadic ovarian carcinomas.Int J Cancer. 2013; 133: 2596-2608https://doi.org/10.1002/ijc.28287
- Hereditary ovarian cancer: a clinicopathological study.Int J Gynecol Pathol. 1992; 11: 180-187
- Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors.Gynecol Oncol. 2011; 121: 462-465https://doi.org/10.1016/j.ygyno.2011.02.010
- The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer.Gynecol Oncol. 2001; 82: 223-228https://doi.org/10.1006/gyno.2001.6279
- Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer.Am J Hum Genet. 2001; 68: 700-710https://doi.org/10.1086/318787
- Phenotypic heterogeneity of hereditary gynecologic cancers: a report from the Creighton hereditary cancer registry.Fam Cancer. 2013; 12: 719-740https://doi.org/10.1007/s10689-013-9651-x
- Screening for familial ovarian cancer: poor survival of BRCA1/2 related cancers.J Med Genet. 2009; 46: 593-597https://doi.org/10.1136/jmg.2008.058248
- Familial ovarian cancer screening.Best Pract Res Clin Obstet Gynaecol. 2006; 20: 321-338https://doi.org/10.1016/j.bpobgyn.2005.10.017
- Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome.N Engl J Med. 2006; 354: 261-269
- Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families.Obstet Gynecol. 2007; 110: 18-25
- Microsatellite instability analysis for the screening of synchronous endometrial and ovarian cancer in Lynch syndrome.Anticancer Res. 2013; 33: 3977-3981
- Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.JAMA. 2011; 305: 2304-2310
- Atypical clustering of gynecologic malignancies: a family study including molecular analysis of candidate genes.Gynecol Oncol. 2000; 77: 18-25
- Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian cancer before age 40.Int J Gynecol Cancer. 2007; 17: 789-793
- Genetic profiles distinguish different types of hereditary ovarian cancer.Oncol Rep. 2010; 24: 885-895
- Risks of less common cancers in proven mutation carriers with lynch syndrome.J Clin Oncol. 2012; 30: 4409-4415
- An Ashkenazi founder mutation in the MSH6 gene leading to HNPCC.Fam Cancer. 2010; 9: 141-150
- Multiple epithelial and nonepithelial tumors in hereditary nonpolyposis colorectal cancer: characterization of germline and somatic mutations of the MSH2 gene and heterogeneity of replication error phenotypes.Cancer Genet Cytogenet. 2004; 153: 108-114
- Reduced frequency of extracolonic cancers in hereditary nonpolyposis colorectal cancer families with monoallelic hMLH1 expression.Am J Hum Genet. 1997; 61: 129-138
- Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members.J Clin Oncol. 2009; 27: 4793-4797
- 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: 1029-1037
- Histologic evaluation of prophylactic hysterectomy and oophorectomy in Lynch syndrome.Am J Surg Pathol. 2013; 37: 579-585
- The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer.Gynecol Oncol. 2014; 133: 526-530
- Gynecologic malignancies in Ashkenazi families with the MSH2 A636P founder mutation.Am J Obstet Gynecol. 2008; 199: 148
- Gynecologic cancer as a “sentinel cancer” for women with hereditary nonpolyposis colorectal cancer syndrome.Obstet Gynecol. 2005; 105: 569-574
- Prevalence of loss of expression of DNA mismatch repair proteins in primary epithelial ovarian tumors.Int J Gynecol Pathol. 2012; 31: 524-531
- Hereditary ovarian cancer. Pedigree studies, Part II.Cancer Genet Cytogenet. 1991; 52: 161-183
- Hereditary ovarian cancer. Heterogeneity in age at diagnosis.Cancer. 1991; 67: 1460-1466
- The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer.Gynecol Oncol. 2006; 101: 238-243
- Chemotherapy resistant ovarian cancer in carriers of an hMSH2 mutation?.Fam Cancer. 2001; 1: 107-109
- Epigenetic analysis of sporadic and Lynch-associated ovarian cancers reveals histology-specific patterns of DNA methylation.Epigenetics. 2014; 9: 1577-1587
- Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.Br J Cancer. 2012; 107: 1783-1790
- Cancer risk in 348 French MSH2 or MLH1 gene carriers.J Med Genet. 2003; 40: 208-213
- A family of five first degree relatives affected by Lynch II syndrome.Hepatogastroenterology. 1994; 41: 417-418
- Multiple synchronous primary ovarian malignancies in a patient with a MLH-1 mutation: impact on potential fertility preservation.Gynecol Oncol. 2011; 121: 637-638
- BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing.Am J Obstet Gynecol. 1998; 178: 670-677
- Consideration of hereditary nonpolyposis colorectal cancer in BRCA mutation-negative familial ovarian cancers.Cancer. 2009; 115: 324-333
- The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study.Am J Hum Genet. 1999; 65: 1725-1732
- Second primary extracolonic cancers in Japanese hereditary nonpolyposis colorectal cancer.Oncol Rep. 1998; 5: 143-145
- Lynch syndrome in patients with clear cell and endometrioid cancers of the ovary.Gynecol Oncol. 2014; 135: 81-84
Published online: January 13, 2016
Accepted: December 6, 2015
Received in revised form: December 1, 2015
Received: July 7, 2015
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.