LOSS OF HETEROZYGOSITY OF BRCA1, TP53 AND TCRD MARKERS ANALYZED IN SPORADIC ENDOMETRIAL CANCER

Genetic alterations of tumour suppressor genes, for which loss of hete rozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the cli nical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluoresc ent DNA technology for the detection of microsatellite polymorphisms w as applied. One hundred and thirteen archival endometrial cancer sampl es with matched normal tissues were examined. Allele loss at three loc i 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, previou s history of cancer or precursor lesions, and previous history of horm one 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 BRCA 1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, posit ive PgR status, and with tumours from patients without HRT; LOH of TCR D correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss o f one of the three tumour suppressor loci did not correlate with disea se-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correl ation 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 end ometrial cancer. (C) 1998 Elsevier Science Ltd, All rights reserved.