Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer.
Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
Niederacher
D
D
Department of Gynaecology and Obstetrics, Heinrich-Heine-Universität, Düsseldorf, Germany.
An
H X
HX
Camrath
S
S
Dominik
S I
SI
Göhring
U J
UJ
Oertel
A
A
Grass
M
M
Hantschmann
P
P
Lordnejad
M R
MR
Beckmann
M W
MW
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism
D019313:BRCA1 Protein; D005819:Genetic Markers; D011948:Receptors, Antigen, T-Cell