Galectin-3在卵巢上皮性肿瘤中的表达及其临床意义
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摘要
卵巢肿瘤是女性生殖系统三大肿瘤之一,其恶性肿瘤死亡率占第一位,且发病范围较广泛,组织学类型繁多,是全身各脏器肿瘤类型最多的器官。卵巢肿瘤的组织学分类主要有4种:卵巢上皮-间质肿瘤、性索-间质肿瘤,生殖细胞瘤及转移性肿瘤。以卵巢上皮-间质肿瘤最常见,可有良性、交界性及恶性之分,其中恶性类型占卵巢恶性肿瘤85%~90%。卵巢上皮性肿瘤发生于育龄及绝经期后的妇女,其发生与长期服用雌激素密切相关,饮食及遗传因素也与其发病的有关。卵巢癌预后较差,五年生存率仅徘徊在30%左右,预后差的原因主要与患者缺少早期症状及有效的诊断方法有关。而且卵巢上皮性癌治疗后的复发率很高,复发癌灶多局限于腹腔脏器的表面,缺乏有效诊断方法,严重威胁妇女健康。因此,有必要寻求一种特异的卵巢上皮性肿瘤标记物以便提高临床和病理诊断水平。
本实验运用免疫组织化学EnVisionTM二步法检测Galectin-3(半乳糖凝集素-3)在卵巢上皮性肿瘤中的表达情况,从而探讨Galectin-3的表达在卵巢上皮性肿瘤诊断中的重要意义。结果显示:Galectin-3主要表达于肿瘤细胞胞质中,少数表达在细胞核及胞膜上;Galectin-3在卵巢囊腺癌中的表达明显高于囊腺瘤及交界性肿瘤(P<0.05);Galectin-3在卵巢浆液性肿瘤与黏液性肿瘤中的表达相似,在良性、交界性及恶性肿瘤中两类上皮的表达均无明显差异(P>0.05);同时发现,Galectin-3在卵巢囊腺癌中的表达强度随着组织学分级、临床分期和转移率的升高而增强,提示Galectin-3可作为判断卵巢癌预后的参考指标。
Ovarian cancer is one of three female reproductive system tumor, the mortality rate of malignant tumour is the first. The incidence range of ovarian cancer is wide and there are many histological typeies and the ovarian cancer is most .Based on cells of different histologic origin: the source of body cavity epithelial ovarian epithelial tumors or tumors, sex cord stromal tumors, germ cell tumors and metastatic tumors. The epithelial ovarian tumor can be divided into benign, borderline, malignant tumors, ovarian cancer accounted for from 85% to 90%.Ovary is located in the deep pelvis, not easily palpable or look up,there is no obvious conscious symptoms, and the patient is often already advanced when seeking medical care.The recurrence rate of ovarian cancer after treatment is high,the recurrence foci more limited surface of intra-abdominal .Over the years, five-year survival rate is only about 30% .A serious threat to women's health. Therefore, it is necessary to search for a specific marker of epithelial ovarian tumors in order to improve the level of clinical and pathological diagnosis.
Galectin-3 also named intracellular and extracellular lectin ,is a molecular weight of 29-35KDaβ-galactosyl glycoside binding protein, which can interact with Intracellular glycoproteins, cell surface molecules and extracellular matrix. The gene is located on chromosome 1P13 and 14q 21-22, which is composed from six exons and five introns. Galectin-3 has the role of regulating cell adhesion, promoting cell proliferation, involving in inflammation、angiogenesis、immune regulation and pre-mRNA splicing,inhibiting apoptosis、promoting tumor invasion and metastasis and so on. Present study shows that Galectin-3 is mainly expressed in the cytoplasm, it can also be found in the nucleus, cell surface or extracellular matrix. With the study of Galectin-3 deepening , the expression of Galectin-3 has been found in a variety of malignant tumor, which contains lung cancer、stomach cancer.、colorectal cancer,、thyroid cancer、breast cancer and malignancies come from central nervous system. currently the reports on Galectin-3 in epithelial ovarian tumor expression is rare.
In this study, we observed the expression of Galectin-3 (Galectin -3) in epithelial ovarian tumors by immunohistochemical EnVisionTM two-step.and explore the important significance of the expression of Galectin-3 in epithelial ovarian neoplasms. The results are as follows: Galectin -3 mianly convey in the tumor cells cytoplasm ,less expressed in the cell nucleus and membrane . In 81 cases with ovarian epithelial tumors, 21 cases with nang adenoma, of which 10 cases with Galectin-3 positive expression, the rate of positive expression is 47.6%; in 12 cases with borderline nang adenoma, Galectin-3 expressed positively in 5 cases, the rate of positive expression is 41.7%; in the 48 cases with nang adenocarcinoma, Galectin-3 expressed positively in 36 cases, the rate of positive expression 75.0%; visible, the positive expression of Galectin-3 in ovarian follicle adenocarcinoma is significantly higher than in the other two types of epithelial tumor (P<0.05). While we compared,the expression of serous tumors and mucinous tumors in benign, borderline and malignant . The results show, the positive expression rate of Galectin-3 in serous Nang adenoma was 55.6%; The positive expression rate of Mucinous Nang adenoma was 41.7%; The difference was not statistically significant (P> 0.05), while the positive expression rate of serous adenocarcinoma Nang was 78.9%, the positive expression rate of mucinous adenocarcinoma Nang was 60.0%, There was no significant difference between the two groups (P> 0.05). It shows that the expression of Galectin-3 has no correlation to the epithelial type in epithelial tumor of ovary. This experiment also observes the expression of Galectin-3 in different histological grading、clinical stages and metastasis of oophoroma. The result shows that the positive expression rate of Galectin-3 is 46.2% in I grade, 81.3% in II grade, 89.5% in III grade. The positive expression rate in II and III grade is significantly higher than I grade, have significant difference (P <0.01). The positive expression rate of Galectin-3 is 58.3% in I period, 68.8% in II period, 90.0% in III period. The positive expression rate in III period is significantly higher than I and II period, have significant difference (P <0.05). The positive expression rate is 86.2% in the group which have metastasised, the positive expression rate is 57.9% in the group which have no metastasised, and have significant difference (P <0.05)between this tow group; It demonstrates that the expression intensity of Galectin-3 enhance with the rising of histological grading、clinical stages and transfer rate in ovarian cystoadenocarcinoma.
In summary, with the histological grade, clinical stage and metastasis rate rising , Galectin-3 in ovarian cystadenomas showed high expression which suggests that Galectin-3 has some significance in prognosis of ovarian cancer , so that clinicians make better prognosis.
本实验运用免疫组织化学EnVisionTM二步法检测Galectin-3(半乳糖凝集素-3)在卵巢上皮性肿瘤中的表达情况,从而探讨Galectin-3的表达在卵巢上皮性肿瘤诊断中的重要意义。结果显示:Galectin-3主要表达于肿瘤细胞胞质中,少数表达在细胞核及胞膜上;Galectin-3在卵巢囊腺癌中的表达明显高于囊腺瘤及交界性肿瘤(P<0.05);Galectin-3在卵巢浆液性肿瘤与黏液性肿瘤中的表达相似,在良性、交界性及恶性肿瘤中两类上皮的表达均无明显差异(P>0.05);同时发现,Galectin-3在卵巢囊腺癌中的表达强度随着组织学分级、临床分期和转移率的升高而增强,提示Galectin-3可作为判断卵巢癌预后的参考指标。
Ovarian cancer is one of three female reproductive system tumor, the mortality rate of malignant tumour is the first. The incidence range of ovarian cancer is wide and there are many histological typeies and the ovarian cancer is most .Based on cells of different histologic origin: the source of body cavity epithelial ovarian epithelial tumors or tumors, sex cord stromal tumors, germ cell tumors and metastatic tumors. The epithelial ovarian tumor can be divided into benign, borderline, malignant tumors, ovarian cancer accounted for from 85% to 90%.Ovary is located in the deep pelvis, not easily palpable or look up,there is no obvious conscious symptoms, and the patient is often already advanced when seeking medical care.The recurrence rate of ovarian cancer after treatment is high,the recurrence foci more limited surface of intra-abdominal .Over the years, five-year survival rate is only about 30% .A serious threat to women's health. Therefore, it is necessary to search for a specific marker of epithelial ovarian tumors in order to improve the level of clinical and pathological diagnosis.
Galectin-3 also named intracellular and extracellular lectin ,is a molecular weight of 29-35KDaβ-galactosyl glycoside binding protein, which can interact with Intracellular glycoproteins, cell surface molecules and extracellular matrix. The gene is located on chromosome 1P13 and 14q 21-22, which is composed from six exons and five introns. Galectin-3 has the role of regulating cell adhesion, promoting cell proliferation, involving in inflammation、angiogenesis、immune regulation and pre-mRNA splicing,inhibiting apoptosis、promoting tumor invasion and metastasis and so on. Present study shows that Galectin-3 is mainly expressed in the cytoplasm, it can also be found in the nucleus, cell surface or extracellular matrix. With the study of Galectin-3 deepening , the expression of Galectin-3 has been found in a variety of malignant tumor, which contains lung cancer、stomach cancer.、colorectal cancer,、thyroid cancer、breast cancer and malignancies come from central nervous system. currently the reports on Galectin-3 in epithelial ovarian tumor expression is rare.
In this study, we observed the expression of Galectin-3 (Galectin -3) in epithelial ovarian tumors by immunohistochemical EnVisionTM two-step.and explore the important significance of the expression of Galectin-3 in epithelial ovarian neoplasms. The results are as follows: Galectin -3 mianly convey in the tumor cells cytoplasm ,less expressed in the cell nucleus and membrane . In 81 cases with ovarian epithelial tumors, 21 cases with nang adenoma, of which 10 cases with Galectin-3 positive expression, the rate of positive expression is 47.6%; in 12 cases with borderline nang adenoma, Galectin-3 expressed positively in 5 cases, the rate of positive expression is 41.7%; in the 48 cases with nang adenocarcinoma, Galectin-3 expressed positively in 36 cases, the rate of positive expression 75.0%; visible, the positive expression of Galectin-3 in ovarian follicle adenocarcinoma is significantly higher than in the other two types of epithelial tumor (P<0.05). While we compared,the expression of serous tumors and mucinous tumors in benign, borderline and malignant . The results show, the positive expression rate of Galectin-3 in serous Nang adenoma was 55.6%; The positive expression rate of Mucinous Nang adenoma was 41.7%; The difference was not statistically significant (P> 0.05), while the positive expression rate of serous adenocarcinoma Nang was 78.9%, the positive expression rate of mucinous adenocarcinoma Nang was 60.0%, There was no significant difference between the two groups (P> 0.05). It shows that the expression of Galectin-3 has no correlation to the epithelial type in epithelial tumor of ovary. This experiment also observes the expression of Galectin-3 in different histological grading、clinical stages and metastasis of oophoroma. The result shows that the positive expression rate of Galectin-3 is 46.2% in I grade, 81.3% in II grade, 89.5% in III grade. The positive expression rate in II and III grade is significantly higher than I grade, have significant difference (P <0.01). The positive expression rate of Galectin-3 is 58.3% in I period, 68.8% in II period, 90.0% in III period. The positive expression rate in III period is significantly higher than I and II period, have significant difference (P <0.05). The positive expression rate is 86.2% in the group which have metastasised, the positive expression rate is 57.9% in the group which have no metastasised, and have significant difference (P <0.05)between this tow group; It demonstrates that the expression intensity of Galectin-3 enhance with the rising of histological grading、clinical stages and transfer rate in ovarian cystoadenocarcinoma.
In summary, with the histological grade, clinical stage and metastasis rate rising , Galectin-3 in ovarian cystadenomas showed high expression which suggests that Galectin-3 has some significance in prognosis of ovarian cancer , so that clinicians make better prognosis.
引文
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[4]Cooper DN, Barondes SH .God must love galectins ; he made so many of them[J] .Glycobiology ,1999,9(10):979-984.
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[2]Barondes SH ,castronoro V , Cooper DN ,et al .Galectins : A Family of animal beta–galactoside-binding lectins[J] Cell ,1994,76(4):597-598.
[3]Perillo NL,Marcus Me,Baum LG,Galectins :versatile modulators of cell adhension ,cell proliferation ,and cell death[J].J Mol Med , 1998,76(6): 402.
[4]Cooper DN, Barondes SH .God must love galectins ; he made so many of them[J] .Glycobiology ,1999,9(10):979-984.
[5]Liffler H. Galectins structure and function–a synopsis[J].Results Probl Cell Differ,2001,33:57-83.
[6]Birdsall B ,Feeney J ,Burdett ID , et al.NMR solution studies of hamster Galectin-3 and electron microscopic visualization of surface-aborbed complexes:evidence for interactions between the N–and C-terminal domains [J].Biochemistry,2001,40:4859 -4866.
[7]Dumic J, Dabelic S ,Flogel M .Galectin-3:an openeded story .Biochim Biophys Acta 2006;1760:616-635.
[8]Poirier F ,Timmons PM, chan CT ,et al, Expression of the L14 lectin during mouse.embryogenesis suggests multiple roles during pre-and post–implantation developoment .Development, 1992,115(1):143-155.
[9]Gitt MA ,Xia YR ,Atchison RE, et al . Sequence ,structure, andchromosomal mapping of the mouse Lgals6 gene ,encoding galectin-6[J] BioL Chem,1998, 273(5):2961-2970.
[10]Chiarotti L, Salvatore P, Frunzio R , et al ,Galectin qenes: regulation of expression [J].Glycoconjugate J, 2004,19(7-9):441-449.
[11]Honjo Y ,Mangia Makker P, Inohara H,el al .Down requlation of Galectin-3 suppress tumorigenicity of human breast carcionoma cells cells .Clin Cancer Res,2001,7:661-668.
[12]Takenaka Y, Fukunori T ,Raz A. Galectin-3 and metastasis[J].Glycoconj J ,2004,19(7-9)543~549.
[13]Moutsatsos IK, Wade M ,Schindler M, et al .Endogenous lectins from cultured cells :nuclear localization of carbohydrate binding protein 35 in proliferating 3T3 fibroblasts [J]. Proc Natl Acad Sci USA ,1987,84:6452.
[14]Sato S ,Hughes RCJ ,Regulation of secretion and surface expression of Mac-2,a galactoside-binding protein of macrophages [J] J Biol Chen,1994, 269:4424.
[15]Yoshii T ,Inohara H.Taskenaka Y , et al. Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cell [J]. Int J Oncol , 2001,18:787~792.
[16]Krzeslak A , Lipinska A. Galectin-3 as a multifunctional protein [J] Cell Mol Biol Lett,2004,9(2):305~328.
[17]Ohannesian DW ,Lotan D ,Thomas P, et al. Carcinoembryonic antigen and other glycocjugates act as ligands for Galectin-3 in human carcinomacell[J].Cancer Res,1995,55:2191~2199.
[18]Inohara H ,Akahani S ,Raz A. Galectin-3 stimulates cell prdiferation [J]Exp Cell Res,1988;245(2)294~302.
[19]Riss D ,Jin L,Qian X , et al. Differential expnession of Galectin-3 in pituitary tumors[J]. cancer Res ,2003;63(9):2251-2255.
[20]Frigeri LG , Iuberi RI, Liu FT.εBP,α,β-galectoside-binding animal lectin ,recognizes IgE receptor and activates mast cells[J] Biochemistry , 1993,32:7644-7649.
[21]Nangia-Makker P ,Honjo Y ,Sarvis R et al. Galectin-3 induces endothe-lial cell morphogenesis and angiogenesis[J]. Am J Pathol, 2000;156 (3)899~909.
[22]Folkman J, Angiogenesis in cancer ,vascular ,rheumatoid and other disease[J].Nat Med ,1995,1(1):27.
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