Expression Of MMP-26 And Its Correlation With ERα, ERβ In Normal, Hyperplastic And Neoplastic Endometrium

Matrix metalloproteinases(MMPs)are important proteolytic enzyme family. Under normal physiological conditions, MMPs play important roles in maintaining the normal menstrual cycle by degradating ECM. In endometrial carcinoma, abnormal expression of MMPs can promote tumor angiogenesis and tumor cell invasion and metastasis, thus promoting the evolution of endometrial cancer. MMP-26 is a new number of MMPs family, its unique structure and activating pattern attract study attention worldwide. Since it was firstly cloned in the cDNA library of human endometrial carcinoma, it was inferred to play important roles in normal menstrual cycle and endometrial cancer development and progession. As with other MMPs, MMP-26 also. As all know, the cyclical changes in normal endometirum and endometrial cancer are closely related with estrogen. Estrogen play biological effects through binding with estrogen receptor. Based on the previous study, the expression of MMP-26, ERαand ERβwas studied in 68 normal, 25 hyperplastic and 44 neoplastic endometriums by immunohistochemistry method. We aim to investigate the distinct role of MMP-26 in normal menstrual cycle and its significance in the development and progression of endometrial cancer. The results are as follows:(1) The expression of MMP-26, ERαand ERβin normal endometrium:1. The expression of MMP-26 was mainly localized in the cytoplasm of the glandular epithelial cells. The expression of MMP-26 began to increase from the early proliferation phase, to the highest in the late proliferarion phase then decreased gradually, and to the lowest in the late secretory phase.2. The expression of ERαwas localized in the nucleus of the glandular epithelium.It showed a persistent high expression level in proliferative phase and began to decrease in early secretory phase, to the lowest in the late secretory phase.3. The expression of ERβwas mainly localized in the nucleus of the glandular epithelium, the cytoplasm also expressed a little. It began to increase from early proliferation, and to the highest in late proliferation, then decreased gradually and to the lowest in the late secretory phase.4. In normal endometrium, the expression of MMP-26 protein had significant correlation with ER (P>0.05); However, the expression of MMP-26 and ERβprotein were positively correlated (P<0.05 ).(2) The expression of MMP-26, ERαand ERβin the endometrial hyperplasia and cancer:1. The expression of MMP-26 was localized in cytoplasm of dysplastic epithelium and cancer cells. The expression of MMP-26 was 76.92% in simple and 100% in complex and atypical hyperplasia respectively; The expression of MMP-26 in endometrial cancer was 54.55%. It significantly decreased comparing to normal and endometrial hyperplasia (P<0.05). Further more, the expression of MMP-26 gradually decreased along with the increase of the histological grade.2. The expression of ERαwas localized in nucleus of dysplasitic glandular epithelium and cancer cells. Its expression in simple, complex and atypical hyperplasia were 84.62%, 80% and 85.71% respectively. In 44 endometrial cancer, the positive rate was 56.82%, which was significantly lower compared with normal and hyperplastic endometrium. The expression of ERαwere 68% and 77.78% in well and moderate differentiated carcinoma, and decreased sharply to 10% in poor differentiated carcinoma (P<0.05).3. The expression of ERβwas mainly localized in nucleus of dysplasia of the glandular epithelium and cancer cells, and less in cytoplasm. The positive expression of MMP-26 was 88% (22/25) in endometrial hyperplasia. The expression of MMP-26 was significantly decreased in endometrial cancer (61.36%, P<0.05) compared with normal and hyperplastic endometrium. In addition, the expression was related to the pathological grade, the higher of the grade, the lower of the expression. 4. The expression of MMP-26 and ERαwere positively correlated in both endometrial hyperplasia and cancer(P<0.05); The expression of MMP-26 and ERβwere negatively correlated in endometrial cancer(P<0.05).In conclusion, the expression of MMP-26, ERαand ERβwere studied in normal, hyperplastic and neoplastic endometriums. It was concluded that the expression of MMP-26 was closely related with estrogen and had a similar expression trend with ERαand ERβ, which demonstrated its potential role in maintaining the normal endometrial menstrual cycles; In endometrial cancer, MMP-26 highly expressed in precancerous and high grade endometrial cancer, its expression was reversely correlated with the pathological grade, the higher of the grade, the lower of the expression. MMP-26 may play an important role in the progression of endometrial cancer, especially from precancerous to cancer, and an important indicator of good prognosis of endometrial cancer.