Abstract Objective To study intensity of Glut  1, COX  2 expression in endometrial adenocarcinoma and precancerous lesions characteristics and its diagnostic value. Using immunohistochemistry SP method detected 20 cases of normal proliferative endometrium, 23 cases of simple endometrial hyperplasia, 21 cases of of complexity endometrial hyperplasia, 43 cases of atypical endometrial hyperplasia, 25 cases of intrauterine pancreatic adenocarcinoma intensity of Glut  1, COX-2 expression. Results of intensity of Glut  1 and COX  2 proliferative endometrium group of positive expression rate in each experimental group and 10.0% the hyperplasia group 0 and 9.1%, the complex hyperplasia group was 4.8% and 14.3%, atypical hyperplasia group of low-level of 20.0% and 25.0%, 52.2% and 52.4%, atypical hyperplasia group of high-level, adenocarcinoma group was 88.0% and 91.7%; intensity of Glut-1, COX  differences among the experimental group was statistically significant (P = 0.000), high level of atypical hyperplasia and endometrial adenocarcinoma group differences were statistically significant (P <0.01). COX  2 and intensity of Glut  1 expression in each group showed a significant positive correlation (P <0.01). Conclusion intensity of Glut  1, COX  2 may play an important role in the development of endometrial cancer, and their combination of high diagnostic value in the differential diagnosis of endometrial adenocarcinoma and precancerous lesions.

Key words endometrial adenocarcinoma intensity of Glut  COX  2

    Endometrial hyperplasia, complex hyperplasia to atypical hyperplasia and endometrial cancer is a continuous spectrum of disease, its occurrence and development mechanism is not yet clear. In this study, using immunohistochemical methods to detect endometrial hyperplasia, atypical endometrial hyperplasia, endometrial adenocarcinoma intensity of Glut-1, COX  2 expression, preliminary to explore intensity of Glut  1, COX  2 in utero membrane cancer development in the sense of its diagnostic value.

    1 Materials and Methods

    1.1 Data

    Collect screening Affiliated Dongfeng Hospital of Yunyang Medical Pathology from January 1999 to December 2003 endometrial samples of 132 cases. (1994) according to the WHO female reproductive system tumor histological type specimens are grouped as follows: 23 cases of simple endometrial hyperplasia, complex endometrial hyperplasia, 21 cases, 20 cases of atypical endometrial hyperplasia of low-level, high level of atypical endometrial hyperplasia of the 23 cases, 25 cases of endometrial adenocarcinoma in the control group (all from the 20 cases of normal proliferative endometrial endometrial lesions full cut of the uterus).

    1.2 Reagents

    Rabbit anti-human intensity of Glut  1 polyclonal antibody, rabbit anti-human COX  2 monoclonal antibody SP kit, DAB chromogenic enzyme substrate, etc. were purchased in Fujian step development of new biotechnology companies.

    1.3 Methods

    Specimens were 10% formalin fixed, paraffin embedded serial sections, thickness 4μm HE staining; immunohistochemical staining SP method, high-pressure boiling antigen retrieval, two markers set the positive and negative controls, respectively. The suspects repeated experiments.

    1.4 Results judge

    The immunohistochemistry results to determine the reference Takahashi et al [1] the intensity of Glut  membrane of tumor cells the the brown fine particles positive cells, COX  2 tumor cell membrane (cytoplasm) appear brown fine particles of positive cells number of positive cells <10% as negative (-), the number of positive cells ≥ 10% as the positive (+).

    1.5 statistical methods

    Use of statistical software SPSS13.0 processing data, Glut  1, COX  2 expression differences between the groups lesions using Pearsonχ2 test, correlation test using Spearman rank correlation analysis between the two.

    2 Results

    2.1 Glut  1, COX  2 expression in each experimental group

    Intensity of Glut  1 positive expression was membrane coloring, as shown in Figure 1,2; COX  2 positive expression in the membrane and cytoplasm are coloring, as shown in Figure 3. Two markers in normal proliferative endometrium, Simple endometrial hyperplasia, the complexity endometrial hyperplasia, low-level atypical endometrial hyperplasia, a high level of atypical endometrial hyperplasia, endometrial glands carcinoma are shown in Table 1. Table 1 Glut  1, COX  2 expression in endometrial tissue

    2.2 Glut  1, COX  2 expression differences in each experimental group

    Glut  1, COX  2 among the experimental group, the differences were statistically significant (χ2 value of 71.799 and 53.379, respectively, P = 0.000); Simple endometrial hyperplasia and the complexity endometrial hyperplasia comparisons were not statistically significant (χ2 values ​​were 1.121 and 0.282, P values ​​were 0.290 and 0.595); comparison between low level of atypical endometrial hyperplasia with high-level atypical endometrial hyperplasia group intensity of Glut  1 difference was statistically significant, COX  2 the difference was not statistically significant (χ2 = 4.740 and 3.228, respectively, P values ​​of 0.029 and 0.072, respectively); high level of atypical endometrial hyperplasia and endometrial adenocarcinoma group difference was statistically significant (χ2 values ​​were 7.442 and 8.839, P values ​​of 0.006 and 0.003, respectively); complex temper in normal proliferative endometrium, simple endometrial hyperplasia with intrauterine no significant difference between the membrane hyperplasia (χ2 values ​​were 2.080 and 0.330, P> 0.05).

    2.3 Glut  1, COX  2 expression in each experimental group

    By the Spearman rank correlation analysis, COX  2 Glut  1 expression was a significant positive correlation (r = of 0.938. EGA revealed that, P = 0.000).

    3 Discussion

    Glucose transporter protein 1 (Glut  1) is a tissue transmembrane transport of glucose carrier, is widely expressed in mammalian embryos and mature organization of low-level basic sugar demand for the organization of cells. The existing studies have shown that upregulation of Glut  1 part of the cancer tissue and cancer at high risk tendencies atypical hyperplasia.

    This study shows, Glut  1 endometrial adenocarcinoma and precancerous lesions showed different degrees of high expression by normal proliferative endometrium, endometrial hyperplasia, complex hyperplasia and low and high levels of atypical hyperplasia, increased gradually to endometrial adenocarcinoma, endometrial cancer and atypical endometrial hyperplasia was significantly higher than in normal proliferative endometrium, a significant difference; with ovarian The results consistent Glut  1 expression observed in the cervix, esophagus and other epithelial tumors from normal tissue to precancerous lesions and was progressively increased to cancer [2]. The study also showed complex hyperplasia and hyperplasia endometrial Glut  1 expression was no significant difference between the high-level atypical hyperplasia endometrial atypical hyperplasia and low-level to endometrial Glut  1 expression significant difference obvious.

    The results of this study by Wang et al [3] conclusions are consistent: intensity of Glut  1 in endometrial cancer, high expression and intensity of Glut  can effectively distinguish between benign endometrium and atypical endometrial hyperplasia with malignant tendency So we think that, Glut  1 abnormal expression may be an early event in the organization malignant transformation. Hypoxic microenvironment, cell glucose absorption and utilization will increase in order to meet its energy requirements, studies have shown that these sugar metabolism increase is mainly through hypoxia-inducible factor  1α (HIF  1α)-mediated hypoxia response gene (HRG) regulation raised Glut  1 expression [4].

    Cyclooxygenase (cyclooxygenase, COX) two isomers: COX  1 is a structural expression of genes involved in the maintenance of physiological functions; COX  2 is induced early immediate response genes not expressed in physiological circumstances or low expression in pathological conditions, can be a variety of cytokine-induced expression. In recent years, studies have shown that COX  2 and tumor development are closely related: in many human tumors, increased expression of COX  2 in tumor mechanism of action is not yet completely clear.

    The results of this study show that COX  2 expression in endometrial adenocarcinoma than atypical endometrial hyperplasia, endometrial hyperplasia, was significantly higher in normal proliferative endometrium, the high level of atypical endometrial hyperplasia The positive expression rate was significantly higher than that of the low-level group, atypical endometrial hyperplasia positive expression rate was significantly higher than that of endometrial hyperplasia (including endometrial hyperplasia and complex hyperplasia) and normal proliferative endometrium, COX  2 expression and the occurrence of endometrial adenocarcinoma important.

    COX  2 may be formed through the stimulation of cell growth, inhibit apoptosis, stimulate neovascularization mediated endometrial cancer [5-induced immune suppression mechanisms. Meanwhile, in the process of the growth of endometrial cancer, the tumor cells release colony-stimulating factor can be re-activated COX  2, to further promote the development of endometrial cancer.

    In summary, Glut  1, COX  positive expression rate of endometrial hyperplasia, atypical endometrial hyperplasia, endometrial adenocarcinoma showed a gradually increasing trend, and COX  2 and the intensity of Glut  a significant positive correlation between 1 expression levels, so we think Glut  1, COX  2 in the development of endometrial adenocarcinoma may jointly play an important role, at the same time, the detection of both endometrial cancer and precancerous expression of endometrial cancer and atypical endometrial hyperplasia lesions have important diagnostic value.