The role of metastasis inducing proteins in endometrial cancer

Abstract

INTRODUCTION Prognosis of women who develop advanced endometrial cancer is poor, with a 5 year survival rate of only 45% and 25% for stages III and IV respectively. Distant metastasis of malignant endometrial cells beyond the primary focus contributes to the advanced disease stages. A group of proteins, known as metastasis-inducing proteins (MIPs), have been shown to induce cellular invasion and metastasis, specifically AGR2, S100A4, S100P and Osteopontin (OPN). METHODS To investigate the expression of these four MIPs in endometrial cancer, and compare it to the endometrium of fertile control and postmenopausal women. Endometrial samples were collected from 55 women; 30 with endometrial cancer, 15 normal fertile control endometrium in the proliferative phase of the cycle and 10 postmenopausal. The expression of MIPs was evaluated by immunohistochemistry and confirmatory testing was undertaken with reverse transcriptase PCR. RESULTS All endometrial cancer samples showed a significantly increased immuno-reactivity to S100P (Stromal, p = 0.0221) and S100A4 (Stromal, p = 0.0275) compared to benign endometrium. However OPN was virtually absent (Glands p = 0.0047, luminal epithelium p=0.0018) in endometrial cancer cells. All postmenopausal samples showed a significantly decreased immuno-reactivity to all the MIPs (OPN, p = 0.0001, S100P, p = 0.0002, AGR2, p > 0.0001, S100A4, p = 0.0004) compared to endometrial cancer cells. RT-PCR results confirmed IHC results for the expression of S100P, AGR2 and S100A4, but contradicted OPN IHC results. The RT-PCR results gained were not statistically significant. DISCUSSION This data provides an interesting insight into the metastatic process of endometrial cancer. My results suggest that all four MIPs play a key role in metastasis of endometrial cancer, in comparison to the normal postmenopausal endometrium. Further research is required to understand the extent of the involvement OPN, S100P, AGR2 and S100A4 in inducing the metastatic process.