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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.
Int J Gynecol Pathol. 2012 May; 31(3):195-205.IJ

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.

Authors+Show Affiliations

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22498935

Citation

Peterson, Lisa M., et al. "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." International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists, vol. 31, no. 3, 2012, pp. 195-205.
Peterson LM, Kipp BR, Halling KC, et al. 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. Int J Gynecol Pathol. 2012;31(3):195-205.
Peterson, L. M., Kipp, B. R., Halling, K. C., Kerr, S. E., Smith, D. I., Distad, T. J., Clayton, A. C., & Medeiros, F. (2012). 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. International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists, 31(3), 195-205. https://doi.org/10.1097/PGP.0b013e318231fc51
Peterson LM, et al. 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. Int J Gynecol Pathol. 2012;31(3):195-205. PubMed PMID: 22498935.
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TY - JOUR T1 - 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. AU - Peterson,Lisa M, AU - Kipp,Benjamin R, AU - Halling,Kevin C, AU - Kerr,Sarah E, AU - Smith,David I, AU - Distad,Tammy J, AU - Clayton,Amy C, AU - Medeiros,Fabiola, PY - 2012/4/14/entrez PY - 2012/4/14/pubmed PY - 2012/10/26/medline SP - 195 EP - 205 JF - International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists JO - Int J Gynecol Pathol VL - 31 IS - 3 N2 - 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. SN - 1538-7151 UR - https://www.unboundmedicine.com/medline/citation/22498935/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_ L2 - https://doi.org/10.1097/PGP.0b013e318231fc51 DB - PRIME DP - Unbound Medicine ER -