Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Moinfar, F; Kremser, ML; Man, YG; Zatloukal, K; Tavassoli, FA; Denk, H.
Allelic imbalances in endometrial stromal neoplasms: frequent genetic alterations in the nontumorous normal-appearing endometrial and myometrial tissues.
GYNECOL ONCOL. 2004; 95(3): 662-671.
Doi: 10.1016/j.ygyno.2004.08.016
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Moinfar Farid
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Zatloukal Kurt
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- Abstract:
- OBJECTIVES: Endometrial stromal sarcoma (ESS) is among the rarest primary malignant tumors of the uterus. The aim of this study was to examine the possibility of loss of heterozygosity (LOH) and microsatellite instability (MIS) in different tissue components of ESS. METHODS AND MATERIALS: Using PCR, we examined DNA extracts from microdissected tissues of 27 uterus samples containing malignant stromal cells of ESS (20 low grade and 3 high grade sarcomas), benign tumor cells of endometrial stromal nodules (ESN, 4 cases) as well as tumor-free myometrial and endometrial tissues close to and distant from the tumors. Normal cervical tissues (epithelial cells, stroma cells) were also microdissected and analyzed. Fifteen polymorphic DNA markers (chromosomes 2p, 3p, 5q, 10q, 11q, 13q, and 17p) were tested to identify possible genetic alterations. Samples from 10 women with prolapsed uteri without any histopathologic abnormalities were also selected as controls. RESULTS: While no genetic alterations could be identified in 12 (44.5%) ESS cases, 15 (55.5%) revealed LOH with at least one polymorphic DNA marker. LOH were found in 3 (100%) high-grade sarcomas, 10 (50%) low-grade ESS, and 2 (50%) benign ESN. Although LOH was found more often in the neoplastic stromal cells, several cases showed concurrent and independent LOH in the tumor-free myometrial or endometrial tissues either close to or distant from the tumors. The most common genetic abnormality (LOH) was observed at PTEN, a tumor suppressor gene located on chromosome 10q. No tumor was associated with microsatellite instability (MSI). The control group without any histologic abnormalities did not show LOH or MSI. CONCLUSIONS: The frequent occurrence of LOH and the lack of MSI suggest that loss of function(s) of tumor suppressor genes and not mismatch repair deficiency plays a key role in the pathogenesis of endometrial stromal neoplasms. The concurrent and independent occurrence of LOH in the stromal tumor cells and the tumor-free and normal-appearing myometrial and endometrial tissues strongly support the concept of genetic alterations in microenvironmental tissues and the interaction(s) between different tissue components in the development and progression of endometrial stromal neoplasms.
- Find related publications in this database (using NLM MeSH Indexing)
- Endometrial Neoplasms - genetics
- Endometrium - physiology
- Female - physiology
- Humans - physiology
- Loss of Heterozygosity - physiology
- Microsatellite Repeats - genetics
- Myometrium - physiology
- PTEN Phosphohydrolase - physiology
- Phosphoric Monoester Hydrolases - genetics
- Sarcoma, Endometrial Stromal - genetics
- Tumor Suppressor Proteins - genetics
- Find related publications in this database (Keywords)
- endometrial stromal sarcoma
- loss of heterozygosity
- genetic alterations in microenvironmental tissues
- PTEN