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Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing.
Cancer 2014; 120(24):3932-9C

Abstract

BACKGROUND

Immunohistochemistry (IHC) for mismatch repair protein expression, microsatellite instability (MSI) testing, tumor morphology, and family history were compared to determine which screening strategy is superior in identifying Lynch syndrome (LS) in unselected women with newly diagnosed endometrial cancer (EC) who have undergone universal germline mutation testing.

METHODS

A prospective cohort study was performed that recruited women with newly diagnosed EC. Participants completed a family history assessment with molecular characterization of EC with IHC and MSI testing and EC assessment for LS-associated morphologic features and underwent universal germline mutation testing for mutations in the mismatch repair pathway. The sensitivity, specificity, and positive and negative predictive values were compared between the screening strategies.

RESULTS

A total of 118 (65%) of 182 consecutive women with EC participated. Of these, 34 women (29%) had tumors that were IHC deficient and 27 women (23%; N = 117) had tumors that were positive for MSI. Twenty women (17%) met IHC criteria and 16 women (15.2%, N = 105) met family history criteria based on Ontario Ministry of Health Criteria for the genetic assessment for LS. Seven women (5.9%) had a germline mutation: 4 had MLH1 (mutL homolog 1), 2 had MSH6 (mutS homolog 6), and 1 had MSH2 (mutS homolog 2). IHC in women aged <60 years had the best performance characteristics, with a sensitivity of 100%, a specificity of 86.1%, a positive predictive value of 58.3%, and a negative predictive value of 100%. Family history and tumor morphology both had the lowest sensitivity at 71.4%. Overall tumor morphology had the poorest performance, with a specificity of 42.1%.

CONCLUSIONS

The mutation rate of 5.9% was higher than expected in this unselected cohort of women with EC. The superior screening strategy to identify women presenting with EC is universal IHC screening in women aged <60 years.

Authors+Show Affiliations

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25081409

Citation

Ferguson, Sarah E., et al. "Performance Characteristics of Screening Strategies for Lynch Syndrome in Unselected Women With Newly Diagnosed Endometrial Cancer Who Have Undergone Universal Germline Mutation Testing." Cancer, vol. 120, no. 24, 2014, pp. 3932-9.
Ferguson SE, Aronson M, Pollett A, et al. Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. Cancer. 2014;120(24):3932-9.
Ferguson, S. E., Aronson, M., Pollett, A., Eiriksson, L. R., Oza, A. M., Gallinger, S., ... Clarke, B. A. (2014). Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. Cancer, 120(24), pp. 3932-9. doi:10.1002/cncr.28933.
Ferguson SE, et al. Performance Characteristics of Screening Strategies for Lynch Syndrome in Unselected Women With Newly Diagnosed Endometrial Cancer Who Have Undergone Universal Germline Mutation Testing. Cancer. 2014 Dec 15;120(24):3932-9. PubMed PMID: 25081409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. AU - Ferguson,Sarah E, AU - Aronson,Melyssa, AU - Pollett,Aaron, AU - Eiriksson,Lua R, AU - Oza,Amit M, AU - Gallinger,Steven, AU - Lerner-Ellis,Jordan, AU - Alvandi,Zahra, AU - Bernardini,Marcus Q, AU - MacKay,Helen J, AU - Mojtahedi,Golnessa, AU - Tone,Alicia A, AU - Massey,Christine, AU - Clarke,Blaise A, Y1 - 2014/07/31/ PY - 2014/04/25/received PY - 2014/06/20/accepted PY - 2014/8/2/entrez PY - 2014/8/2/pubmed PY - 2015/2/26/medline KW - Lynch syndrome KW - endometrial cancer KW - germline mutation testing KW - immunohistochemistry KW - mismatch repair SP - 3932 EP - 9 JF - Cancer JO - Cancer VL - 120 IS - 24 N2 - BACKGROUND: Immunohistochemistry (IHC) for mismatch repair protein expression, microsatellite instability (MSI) testing, tumor morphology, and family history were compared to determine which screening strategy is superior in identifying Lynch syndrome (LS) in unselected women with newly diagnosed endometrial cancer (EC) who have undergone universal germline mutation testing. METHODS: A prospective cohort study was performed that recruited women with newly diagnosed EC. Participants completed a family history assessment with molecular characterization of EC with IHC and MSI testing and EC assessment for LS-associated morphologic features and underwent universal germline mutation testing for mutations in the mismatch repair pathway. The sensitivity, specificity, and positive and negative predictive values were compared between the screening strategies. RESULTS: A total of 118 (65%) of 182 consecutive women with EC participated. Of these, 34 women (29%) had tumors that were IHC deficient and 27 women (23%; N = 117) had tumors that were positive for MSI. Twenty women (17%) met IHC criteria and 16 women (15.2%, N = 105) met family history criteria based on Ontario Ministry of Health Criteria for the genetic assessment for LS. Seven women (5.9%) had a germline mutation: 4 had MLH1 (mutL homolog 1), 2 had MSH6 (mutS homolog 6), and 1 had MSH2 (mutS homolog 2). IHC in women aged <60 years had the best performance characteristics, with a sensitivity of 100%, a specificity of 86.1%, a positive predictive value of 58.3%, and a negative predictive value of 100%. Family history and tumor morphology both had the lowest sensitivity at 71.4%. Overall tumor morphology had the poorest performance, with a specificity of 42.1%. CONCLUSIONS: The mutation rate of 5.9% was higher than expected in this unselected cohort of women with EC. The superior screening strategy to identify women presenting with EC is universal IHC screening in women aged <60 years. SN - 1097-0142 UR - https://www.unboundmedicine.com/medline/citation/25081409/Performance_characteristics_of_screening_strategies_for_Lynch_syndrome_in_unselected_women_with_newly_diagnosed_endometrial_cancer_who_have_undergone_universal_germline_mutation_testing_ L2 - https://doi.org/10.1002/cncr.28933 DB - PRIME DP - Unbound Medicine ER -