Gene Expression in Primary, Metastatic and Recurrent Lesions of Endometrial Cancer

Abstract

Seventeen patients with endometrial cancer were studied. Tissues of primary (P) and metastatic (M) lesions were obtained from 8 patients and complete sets of P, M and Recurrent (R) lesions were obtained from 9 patients during a follow-up period of 1-10 years. Expressions of estrogen receptors, progesterone receptors, multidrug resistance protein-1, multidrug resistance-related protein, c-erbB-2, membrane-type metalloproteinase, human telomerase RNA, human telomerase reverse transcriptase RNA, E-cadherin and autocrine motility factor receptor were studied by RT-PCR. Also, telomeric restriction fragment length (TRFL) and microsatellite instability were determined between P, M and R. The results indicate that there are significant differences in the gene expression frequency during tumor progression. The mismatch rate ranged from 0 to 47.1% between P and M and from 14.3% to 66.7% between P and R, respectively. The TRFL analysis showed a marked reduction in P and M (P vs. M: 8.2 +/- 0.9 vs. 5.6 +/- 0.4 kb, mean +/-SEM, n = 9, p = 0.002 by paired Student's t test). The length further decreased in R (P vs. R: 8.2 +/- 0.9 vs. 3.2 +/- 0.7, p = 0.01, M vs. R: 5.6 +/- 0.4 vs. 3.2 +/- 0.7, p = 0.005). The genomic instability/replication error was tested by AluI arbitrary primed polymerase chain reaction (AP-PCR). Five out of 17 patients showed an altered replication error pattern (29.4%). The mean number of abnormal AluI AP-PCR patterns in M and R compared to the P was 1.5 (M) and 4 (R). The difference between the P and R was statistically significant (p < 0.04). The present data indicate that biological behavior of cancer cells in P, M and R may differ significantly.