Utility of MLH1 methylation analysis in the clinical evaluation of lynch syndrome in women with endometrial cancer

Amanda Bruegl, Bojana Djordjevic, Diana L. Urbauer, Shannon N. Westin, Pamela T. Soliman, Karen H. Lu, Rajyalakshmi Luthra, Russell R. Broaddus

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

Original languageEnglish (US)
Pages (from-to)1655-1663
Number of pages9
JournalCurrent Pharmaceutical Design
Volume20
Issue number11
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Hereditary Nonpolyposis Colorectal Neoplasms
Endometrial Neoplasms
Methylation
Microsatellite Instability
DNA Mismatch Repair
Immunohistochemistry
Polymerase Chain Reaction
Mutation

Keywords

  • Endometrial câncer
  • Immunohistochemistry
  • Lynch syndrome
  • MLH1 methylation
  • Molecular diagnostics

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

Cite this

Utility of MLH1 methylation analysis in the clinical evaluation of lynch syndrome in women with endometrial cancer. / Bruegl, Amanda; Djordjevic, Bojana; Urbauer, Diana L.; Westin, Shannon N.; Soliman, Pamela T.; Lu, Karen H.; Luthra, Rajyalakshmi; Broaddus, Russell R.

In: Current Pharmaceutical Design, Vol. 20, No. 11, 2014, p. 1655-1663.

Research output: Contribution to journalArticle

Bruegl, A, Djordjevic, B, Urbauer, DL, Westin, SN, Soliman, PT, Lu, KH, Luthra, R & Broaddus, RR 2014, 'Utility of MLH1 methylation analysis in the clinical evaluation of lynch syndrome in women with endometrial cancer', Current Pharmaceutical Design, vol. 20, no. 11, pp. 1655-1663. https://doi.org/10.2174/13816128113199990538
Bruegl, Amanda ; Djordjevic, Bojana ; Urbauer, Diana L. ; Westin, Shannon N. ; Soliman, Pamela T. ; Lu, Karen H. ; Luthra, Rajyalakshmi ; Broaddus, Russell R. / Utility of MLH1 methylation analysis in the clinical evaluation of lynch syndrome in women with endometrial cancer. In: Current Pharmaceutical Design. 2014 ; Vol. 20, No. 11. pp. 1655-1663.
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