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Gynecol Oncol. 2014 Aug;134(2):319-25. doi: 10.1016/j.ygyno.2014.06.009. Epub 2014 Jun 14.

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

Author information

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 2Department of Pathology and Laboratory Medicine, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada.
  • 3Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 4Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 5Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.

KEYWORDS:

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

PMID:
24933100
PMCID:
PMC4125501
DOI:
10.1016/j.ygyno.2014.06.009
[PubMed - indexed for MEDLINE]
Free PMC Article
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