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High concordance of molecular tumor alterations between pre-operative curettage and hysterectomy specimens in patients with endometrial carcinoma.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2014 May; Vol. 133 (2), pp. 197-204. Date of Electronic Publication: 2014 Feb 18. - Publication Year :
- 2014
-
Abstract
- Objective: Molecular alterations in endometrial cancer have been shown to be prognostically significant but have not yet been implemented in the current clinical risk assessment. Few studies have investigated the reliability of molecular alterations in pre-operative specimens. Therefore, the objective was to determine whether molecular analysis of pre-operative endometrial cancer samples accurately reflects those alterations in the subsequent hysterectomy specimens.<br />Methods: Paired pre-operative and hysterectomy specimens of 48 patients diagnosed with endometrial carcinoma, 42 endometrioid (EEC) and 6 non-endometrioid (NEEC) carcinomas, were analyzed for immunohistochemical expression of p53, PTEN and β-catenin. Tumor DNA was isolated and analyzed for microsatellite instability (MSI), TP53 mutations and somatic hot spot mutations in 13 genes.<br />Results: In EEC patients, loss of PTEN, nuclear β-catenin and p53-mutant expression was found in 43%, 7% and 12%, respectively. No nuclear β-catenin was found in 5 of 6 NEEC patients, all serous cancers, whereas a p53-mutant expression was present in all serous cases. MSI was found in 19.5%, all EEC. Concordance for PTEN, β-catenin, p53 expression and MSI status was found in 79%, 92%, 79% and 93.5%, respectively. We detected 65 hot spot mutations in 39/48 (81%) tumors. Overall concordance of the GynCarta multigene analysis was 99.8%.<br />Conclusions: The results confirm the reliability of immunohistochemical and DNA-based techniques in the evaluation of molecular alterations in pre-operative endometrial specimens and high concordance rates with the definitive hysterectomy specimens. The resulting molecular signature provides initial pre-operative diagnostic information on the status of oncogenic pathways, which may contribute to individualized treatment strategies.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Biomarkers, Tumor metabolism
Biopsy
Carcinoma, Endometrioid metabolism
Carcinoma, Endometrioid pathology
Carcinoma, Endometrioid surgery
Endometrial Neoplasms metabolism
Endometrial Neoplasms pathology
Endometrial Neoplasms surgery
Female
Genes, p53 genetics
Genetic Markers
Humans
Immunohistochemistry
Microsatellite Instability
Middle Aged
Mutation
PTEN Phosphohydrolase metabolism
Reproducibility of Results
beta Catenin metabolism
Biomarkers, Tumor genetics
Carcinoma, Endometrioid genetics
Curettage
DNA, Neoplasm analysis
Endometrial Neoplasms genetics
Hysterectomy
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 133
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24556061
- Full Text :
- https://doi.org/10.1016/j.ygyno.2014.02.012