The Expression And Significance Of Biglycan In Endometrial Carcinoma

ObjectiveEndometrial carcinoma is one of the three worst cancers in reproductive system. The number of women with newly diagnosed has increased in these years. In common with other cancers, endometrial carcinoma also shows disorder of control elements, imbalance of growth and death, which result in abnomal proliferation and incidence of cancer. Biglycan(BGN), as a component of extracellular matrix, is a member of class I small leucine-rich proteoglycans(SLRPs). Biglycan is thought to be the result of a gene duplication. It has a wide distribution in bones, gristles, fibrous tissues and periodontium tissues. Recent studies showed that Biglycan is overexpressed in osteogenic sarcoma and colorectal carcinoma, which reveals that it is closely related to the incidence of cancer. Untill now there is no report shows biglycan expression in endometrial carcinoma. In this purpose, transcription and protein levels in endometrial cancer tissues and cells were tried to investigate the expressions of Biglycan.MethodsImmunohistochemistry method was used to detect the expressions of Biglycan in paraffin-embedded tumor samples from 10 normal endometrial tissue,10 atypical hyperplasia endomembrane and 53 endometrial cancers, and discuss its relationship with clinical significance and prognosis in the development of endometrial carcinoma. 53 cases of endometrial surgical paraffin-embedded tissues wre collected from 2002 to 2007 in pathology department of Qilu hospital of Shandong University. On the basis of histological type, there are 41 Endometrioid,4 Adenosquamous,4 Serous papillary,3 Clear cell and 1 Squamous cell. According to the standard of FIGO 2000 surgical stage, there are 30 Stage I,7 StageⅡ,15 StageⅢand 1 Stage IV. Judging by histological grade,15 are of grade I,21 are of gradeⅡand 17 are of gradeⅢ. At the same time, we used 10 normal endometrial tissues,10 atypical hyperplasia endomembrane as control.Real-time RT-qPCR was used to detect the expression of Biglycan mRNA in fresh tissues of 3 atypical hyperplasia endomembrane and 12 endometrial cancers. Take fresh cancer tissues and tissues beyond 5cm of surgery boundary in operation room, put in liquid nitrogen immediately and then transfer into-80℃freezer for reverse transcription.Western Blot was used to detect the expreesion of Biglycan in 5 endometrial cancer cell lines. Among these cell lines, ECC-1 is well-differentiated, HEC-1A and RL95-2 are moderately-differentiated, KLE and AN3CA are poorly-differentiated. At the same time, use Hepatocarcinoma cell line HepG2 as positive control.Results(1) The expressions of Biglycan in normal endometrial tissues, atypical hyperplasia endomembranes and endometrial cancersThe positive staining of Biglycan is the color of sepia in cytoplasm. Biglycan showed negative expressions in normal endometrial tissues and negative or weak positive in atypical hyperplasia endomembranes. The expression score was 1.09±0.86 in endometrial cancer cells and 1.32±0.86 in carcinomatous mesenchyme, which had no significance (P>0.05).(2) The relationships of the expressions of Biglycan and various clinical indicatorsThe expression of Biglycan had no significant relations with histological type and FIGO surgical stage(P>0.05). In histological grades, there were no significant differences in cancer cell. But the expression in grade III was significantly higer than that in grade I and gradeⅡ(P<0.05).(3) The relationships of the expressions of Biglycan and prognosisAccording to the statics of follow-up data, the patients of positive expression of Biglycan had bad prognosis than that of negative expression in survival curve using the score of 1.8 as boundary(P<0.05).(4) The results of Real-time PCR shows the expression of Biglycan mRNA in endometrial cancer is significantly higher than that in atypical hyperplasia endomembranes (P<0.05).(5) The results of Western Blot shows high level expression in ECC-1 and KLE cell lines, low expression in AN3CA and HEC-1A cell lines, which are ready for gene transfection.Conclusion(1) Biglycan may serve as a oncogene in endometrial carcinoma. The abnomal expression of Biglycan probably play an important role in the development of endometrial carcinoma through Carcinomatous Stroma.(2) The expression of Biglycan in Carcinomous Stroma relates to the histologic grade and the poor prognosis of endometrial carcinomarognosis. Therefore, Biglycan can serve as a prognostic factor.