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.

Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer

“…We found that PR expression decreased significantly with increasing disease severity. This conclusion is consistent with many previous reports that loss of PR expression correlates with advanced disease [ 37 , 38 ]. Next, we investigated the mechanisms which contribute to PR loss.…”

Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion

“…In the current study, MT1‐MMP protein was mainly localized to neoplastic epithelial cells, as also reported in lung and gastric carincomas 24, 25. The current data support previous studies showing that endometrial tumor cells are the main producers of MT1‐MMP mRNA in endometrial carcinoma26 and that high MT1‐MMP gene expression in primary endometrial carcinoma tissue correlates with MT1‐MMP expression in metastatic lesions 27. We observed a correlation of MT1‐MMP protein expression with both increasing depth of myometrial invasion and the presence of vascular/lymphatic invasion.…”

Progesterone receptor A and B expression and progestagen treatment in growth and spread of endometrial cancer cells in nude mice

“…During progression of endometrial cancer, the expression of PR is decreased (Arnett-Mansfield et al 2001, Fujimoto et al 1995, Fukuda et al 1998, Kumar et al 1998, Sakamoto et al 1999. Although it remains unclear whether this is a consequence of down-regulation of only one PR isotype or both, several studies suggest that relative over-expression of PRB is associated with more aggressive tumour growth.…”