Il - 18 In Breast Cancer And Expression In Nsclc, And The Correlation Of Il - 10

In our country,with the incidence of breast cancer rising rapidly,this malignant tumorhas become a serious threat to women’s lives and health. Although we have made greatprogresses in surgery,adiotherapy,chemotherapy and endocrine therapy, there are still noteffective treatment methods for advanced and metastatic breast cancer.With thedevelopment of molecular biology, cell biology and immunology, biological immunetherapy has become a new way for cancer treatment.IL-18was found by Okamura in1995. It often exists as an active precursor mode andplay biological activities only after cutting by Interleukin1-beita invertase (Interleukin1-beita converting enzyme, ICE).The structure of IL-18is similar to interleukin-1,withIL-1characteristic structure F-X (12)-F-X-S-X (6)-F-L series. Both IL-18and IL-1have nohydrophobic signal peptide sequence in N-end of precursor molecules, instead of a periodof no functional leading sequence.IL-18can induce IFN-r,and participate in resistanceintracellular infection parasites.Studies confirmed that tumor cell lines PG of transfectedIL-18genes has declined tumorigenicity in the same mices, slowed the tumor growth, andextended survival time. However, some cell lines such as AsPC-1cells of transfected IL-18genes has not changed tumorigenicity, and tumor growth speed is identical with wild type.And some studies showed that serum IL-18levels are increased in some cancers, andassociated with some poor prognotic factors.IL-10is a35-40kD protein discoveried by Fiorentino in1989,whose active form is anon-covalentbond connected oligo-dimer.IL-10is a multifunctional cytokine,and secretedby Th2.It plays an important role in the process of controlling cellular immunity,inhibittingthe production of proinflammatory factor secretion. Studies have showed that IL-10caninhibit the activation of T cells, especially inhibit Th1cells to produce IL-2,IFN-γ,restrainCTL and NK cells to damage tumor cells, restrain dendritic cells to present antigen andinduce T cells immune tolerance.Studies showed that IL-10was a poor pronostic factor incancers. Up to now, little was known about IL-18expression in cancer tissues and itsrelationship with IL-10.In this study, we examined IL-18expression in104primary breastcancer tissues by immunohistochemical staining and analyze its relationship withclinicopathologic data.To investigate the new potential machenism of breast cancerdevelopment.The relationship between IL-10and IL-18expression was also done.Objective:To investigate the expression of IL-18in primary breast cancer tissues,and analyze therelationship between IL-18expression and the clinical parameters and IL-10expression.Methods:Applying the immunohistochemical Elivision method, expression of IL-18wasdetected in104breast carcinoma tissues and31fibroadenoma of the breast tissues.Therelationship between IL-18and the clinicopathological features of breast carcinoma wasthen analyzed. The relationship between IL-10and IL-18expression was also done.Results:1. In most spemcimens,the patterns of IL-18expression appeared to be very diffuseacross the section. Microscopically, IL-18was found in the cell membrane, cytoplasm, orboth.75.00%（78/104）expressed IL-18in primary breast cancer tissues, which wassignificantly higer than that（19.4%）of fibroadenoma of the breast tissue.（P＜0.05）.2. Like IL-18,the patterns of IL-10expression was very diffuse throughout the sectionin most cases.78.80%(82/104)of primary breast cancer tissues expressed IL-10,which wassignificantly higer than that（22.6%）of fibroadenoma of the breast tissue.（P＜0.05）.3. The expression of IL-10was significantly correlated with the expression of IL-18in primary breast cancer tissues（r2=0.284,P＜0.05）.4. Both IL-10and IL-18expression are positively correlated with lymph nodemetastasis in primary breast cancer（IL-18：P=0.035；IL-10：P=0.047）.However, therewas no relationship them and other clinical pathological parameters such as age, tumor size,histological grade, differentiation grade, TNM stage,ER,PR status and HER-2expression.Conclusion:IL-18showed higher expression in primary breast cancer tissues. And its expressionwas positively related with IL-10in the tumor tissues. Patients with high expression ofIL-18or IL-10were more likely to have lymph node metastasis. That means highexpression of IL-18, like IL-10, in breast cancer cells may play a role in the primary breastcancer progression and invasiveness. Non-small cell lung cancer is the most common type of lung cancer, accounting forapproximately80%of cases. Althrough patients are treated with chemotherapy and/orradiotherapy, the median survival time in advanced NSCLC remains very poor. Thus, thereis a need to identify new therapeutic strategies for NSCLC that does not respond to currenttreatment options。IL-18was found by Okamura in1995. It was produced by mononuclear phagocytes orsome epithelias. The structure of IL-18is similar to interleukin1, with IL-1characteristicstructure F-X (12)-F-X-S-X (6)-F-L series. Both IL-18and IL-1have no hydrophobicsignal peptide sequence in N-end of precursor molecules, instead of a period of nofunctional leading sequence. IL-18can induce IFN-γ,and participate in resistanceintracellular infection parasites. Studies confirmed that tumor cell lines PG of transfectedIL-18genes has declined tumorigenicity in the same mices, slowed the tumor growth, andextended survival time. However, some cell lines such as AsPC-1cells of transfected IL-18genes has not changed tumorigenicity, and tumor growth speed is identical with wild type.IL-18can promote CTL apoptosis. And some studies showed that serum IL-18levels areincreased in some cancers, and associated with some poor prognotic factors.Interleukin-10is a single, glycoprotein, produced by T h2cells. Some other cells,such as, TH0cells, CD8+T cells, activated the B cell, Kufpper cells, liver cells, hepaticstellate cells (HSC), can also produce IL-10. IL-10plays an important role in keeping thebalance of the cytokine network. Researches proved that interleukin-10can inhibit tumorgrowth and confront tumor transferring, which can restrain DC to be mature, andparticipate in multiple disease pathophysiological processes. Studies showed that serumIL-10and IL-18levels in NSCLC were significantly higher than corresponding normalspecimens.Up to now, little was known about IL-18expression in cancer tissues and itsrelationship with IL-10. In this study, we examined IL-18expression in82primaryNSCLC tissues by immunohistochemical staining and analyze its relationship withclinicopathologic data.To investigate the new potential machenism of NSCLCdevelopment, The relationship between IL-10and IL-18expression was also done. Objective:To detect the expression of IL-18in primary NSCLC tissues,and analysis therelationship between IL-18expression and the clinical parameters and IL-10expression.Methods:Applying the immunohistochemical Elivision method, expressions of IL-18wasdetected in82primary NSCLC tissues and20adjacent normal tissues.The relationshipbetween IL-18and clinicopathologic data was then analyzed.The relationship betweenIL-10and IL-18expression was also done.Results:1. In most spemcimens, the patterns of IL-18expression appeared to be very diffuseacross the section. Microscopically, IL-18was found in the cell membrane, cytoplasm, orboth, while some adjacent normal lung tissues expressed IL-18.73.10%expressed IL-18inprimary NSCLC tissues, which was significantly higer than that (15%) of adjacent normallung tissues.(P＜0.05)2. Like IL-18,the patterns of IL-10expression was very diffuse throughout the sectionin most cases.65.85%of primary NSCLC expressed IL-10,which was significantly higerthan that (15%) of adjacent normal lung tissues.(P＜0.05)3. The expression of IL-18was significantly correlated with the expression of IL-10in primary NSCLC tissues.(R2=0.443,P＜0.05）4. Both IL-18and IL-10expression are positively correlated with lymph nodemetastasis and differentiation grade in primary NSCLC.However, there was no relationshipthem and other clinical pathological parameters such as age, tumor size,histological type,TNM stage and so on.Conclusion:IL-18showed higher expression in primary NSCLC tissues. And Its expression waspositively related with IL-10in the tumor tissues, Patients with high expression of IL-18orIL-10were more likely to have lymph node metastasis and low differentiation grade. Thatmeans high expression of IL-18, like IL-10,in NSCLC cells may play a role in the primaryNSCLC progression and invasiveness.