DNA mismatch repair and TP53 defects are early events in uterine carcinosarcoma tumorigenesis. Mod Pathol 2006 Oct;19(10):1333-8
Date
07/01/2006Pubmed ID
16810312DOI
10.1038/modpathol.3800654Scopus ID
2-s2.0-33748853554 (requires institutional sign-in at Scopus site) 58 CitationsAbstract
Growing molecular evidence shows that uterine carcinosarcomas are clonal tumors. The carcinoma component has a dominant effect in the aggressive clinical behavior of these tumors. Defective DNA mismatch repair affects up to 30% of endometrial adenocarcinomas. The frequency and importance of defective DNA mismatch repair in the histiogenesis of uterine carcinosarcomas remains controversial. We studied the pattern and frequency of defective DNA mismatch repair and TP53 alterations in the epithelial and mesenchymal components of 28 uterine carcinosarcomas. We found evidence of defective DNA mismatch repair in six cases (21%) with a concordance rate of 83% for carcinoma-sarcoma pairs (kappa=0.887, P<0.001). Lack of immunostaining for the MLH1 protein was demonstrated in both components in two of these tumors. TP53 defects were evaluated by 17p deletion analysis and p53 immunostaining. Nineteen carcinoma (68%) and 18 sarcoma (64%) components had evidence of either TP53 allelic loss or p53 overexpression. These defects proved clonal in 76% of cases (kappa=0.602, P=0.003). Our results indicate that defective DNA mismatch repair and TP53 defects are common early events in carcinosarcoma tumorigenesis. The high rate of concordance for these molecular defects between the carcinoma and sarcoma components adds to existing molecular evidence that carcinosarcomas are clonal malignancies.
Author List
Taylor NP, Zighelboim I, Huettner PC, Powell MA, Gibb RK, Rader JS, Mutch DG, Edmonston TB, Goodfellow PJAuthor
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAged
Base Pair Mismatch
Carcinosarcoma
Carrier Proteins
Cell Transformation, Neoplastic
Chromosomal Instability
DNA Repair
DNA, Neoplasm
DNA-Binding Proteins
Female
Humans
Immunohistochemistry
Loss of Heterozygosity
Microsatellite Repeats
MutL Protein Homolog 1
MutS Homolog 2 Protein
Nuclear Proteins
Retrospective Studies
Tumor Suppressor Protein p53
Uterine Neoplasms