Molecular characterization of endometrial cancer: A correlative study assessing microsatellite instability, MLH1 hypermethylation, DNA mismatch repair protein expression, and PTEN, PIK3CA, KRAS, and BRAF mutation analysis

Lisa M. Peterson, Benjamin R. Kipp, Kevin C. Halling, Sarah E. Kerr, David I. Smith, Tammy J. Distad, Amy C. Clayton, Fabiola Medeiros

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Endometrial cancer is associated with numeric and structural chromosomal abnormalities, microsatellite instability (MSI), and alterations that activate oncogenes and inactivate tumor suppressor genes. The aim of this study was to characterize a set of endometrial cancers using multiple molecular genetic and immunohistochemical techniques. Ninety-six cases were examined for genomic alterations by MSI, MLH1 promoter hypermethylation, p53 and mismatch repair protein expression (MLH1, MSH2, MSH6, PMS2), and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. At least 1 alteration was identified in 48 of 87 (55%) specimens tested for PTEN, making it the most common abnormality in this study. A PIK3CA alteration was observed in 16 (17%) specimens. Twenty-nine of 94 (31%) MSI tested tumors exhibited an MSI-H phenotype. Of the 29 MSI-H cases, 24 (83%) were positive for methylation of the MLH1 promoter region. Twenty-three (82%) of the 28 MSI-H cases with immunohistochemistry results showed loss of expression of MLH1/PMS2 (n=19), MSH2/MSH6 (n=2), or MSH6 only (n=2). Of the 19 MSI-H cases with loss of MLH1/PMS2 on immunohistochemistry, 18 were positive, and 1 was equivocal for MLH1 promoter hypermethylation. Twelve of 94 cases (13%) analyzed for KRAS mutations were found to have a mutation. No BRAF V600E mutations were indentified. This study provides a comprehensive molecular genetic analysis of commonly analyzed targets in a large cohort of endometrial cancers.

Original languageEnglish (US)
Pages (from-to)195-205
Number of pages11
JournalInternational Journal of Gynecological Pathology
Volume31
Issue number3
DOIs
StatePublished - May 1 2012

Keywords

  • Carcinosarcoma
  • Clear cell
  • Endometrioid
  • Sequencing
  • Serous

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Obstetrics and Gynecology

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