Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome

Brittany A L Batte, Amanda Bruegl, Molly S. Daniels, Kari L. Ring, Katherine M. Dempsey, Bojana Djordjevic, Rajyalakshmi Luthra, Bryan M. Fellman, Karen H. Lu, Russell R. Broaddus

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47 Citations (Scopus)

Abstract

Objective Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. Methods The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. Results In the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage. Conclusions There are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.

Original languageEnglish (US)
Pages (from-to)319-325
Number of pages7
JournalGynecologic Oncology
Volume134
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

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Hereditary Nonpolyposis Colorectal Neoplasms
Early Detection of Cancer
Genetic Counseling
Genetic Testing
Neoplasms
Endometrial Neoplasms
Microsatellite Instability
Germ-Line Mutation
Methylation
DNA Mismatch Repair
Insurance Coverage
N-methylsuccinimide
Immunohistochemistry

Keywords

  • Cancer risk
  • DNA mismatch repair
  • Endometrial cancer
  • Genetic counseling
  • Lynch syndrome
  • Screening

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Batte, B. A. L., Bruegl, A., Daniels, M. S., Ring, K. L., Dempsey, K. M., Djordjevic, B., ... Broaddus, R. R. (2014). Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome. Gynecologic Oncology, 134(2), 319-325. https://doi.org/10.1016/j.ygyno.2014.06.009

Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome. / Batte, Brittany A L; Bruegl, Amanda; Daniels, Molly S.; Ring, Kari L.; Dempsey, Katherine M.; Djordjevic, Bojana; Luthra, Rajyalakshmi; Fellman, Bryan M.; Lu, Karen H.; Broaddus, Russell R.

In: Gynecologic Oncology, Vol. 134, No. 2, 2014, p. 319-325.

Research output: Contribution to journalArticle

Batte, BAL, Bruegl, A, Daniels, MS, Ring, KL, Dempsey, KM, Djordjevic, B, Luthra, R, Fellman, BM, Lu, KH & Broaddus, RR 2014, 'Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome', Gynecologic Oncology, vol. 134, no. 2, pp. 319-325. https://doi.org/10.1016/j.ygyno.2014.06.009
Batte, Brittany A L ; Bruegl, Amanda ; Daniels, Molly S. ; Ring, Kari L. ; Dempsey, Katherine M. ; Djordjevic, Bojana ; Luthra, Rajyalakshmi ; Fellman, Bryan M. ; Lu, Karen H. ; Broaddus, Russell R. / Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome. In: Gynecologic Oncology. 2014 ; Vol. 134, No. 2. pp. 319-325.
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abstract = "Objective Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. Methods The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. Results In the retrospective cohort, 11{\%} had tumor studies suggestive of Lynch syndrome, and 42{\%} was seen for genetic counseling. A germline mutation was detected in 40{\%}, and one had a variant of uncertain significance. In the prospective cohort, 8.7{\%} of patients had tumor testing suggestive of Lynch syndrome; 72{\%} were seen for genetic counseling. Germline mutations were found in 40{\%}, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage. Conclusions There are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.",
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AU - Bruegl, Amanda

AU - Daniels, Molly S.

AU - Ring, Kari L.

AU - Dempsey, Katherine M.

AU - Djordjevic, Bojana

AU - Luthra, Rajyalakshmi

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AU - Lu, Karen H.

AU - Broaddus, Russell R.

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N2 - Objective Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. Methods The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. Results In the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage. Conclusions There are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.

AB - Objective Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. Methods The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. Results In the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage. Conclusions There are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.

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