Expression And Significance Of Leptin And Matrix Metalloproteinase-2 In Gastric Carcinoma

Background and objective:The gastric carcinoma(GC) is one of malignant tumors,it seriously harms the human beings' lives.It's incidence is the first of digestive canal cancers,the fouth of all cancers,it's case-fatality rate is the second of all cancers.Two-third of GC patients are in the developing countries,42 percent of them are in China. There are two tough problems in clinic therapy : infiltration and aversion ,they are also lethal factors for most patients.Therefore,it is still a hot study point on how to elevate diagnosis rate at early stage and monitor its aversion. Leptin is a product coded by the obesity gene and mainly secreted by the fat, which plays a important role in the process of regulating food-uptake,energy-metabolism and sustaining the body weight balance. Precent investigations show that leptin can prohibit the apoptosis of tumor cells, stimulate their proliferation, promote their invasion ability into the basic membrane and facilitate the vescular formation, which are closely related to the happeningand development of the various malignant tumors.At present ,it is still unknown what is the effect of leptinon the happening and development of GC.The matrix metalloproteinase-2 is a member of the MMP family, It can dissolve extracellular matrix as collagenase ,it can also facilitate the vescular formation of the tumor,which has a importent effect on the growth and transfering procession of tumor. Some studies show that leptin can up-regulate the expression of MMP-2 and they two educe a synergistic effect in the development of GC.This study detects the expression of leptin and MMP-2 proteinum in the stomach mucosa pathological changes tissus in different stages by means of theimmunohistochemistry ,to approach the effect and interrelation of them in the happening, infiltrating and transfering of GC.It provids a new rationale to the early diagnosis, clinical prevention and cure and judgement of prognosis of GC.Materials and methods:1. 19 cases of normal gastric mucosa(NGM), 19 cases of chronic atrophic gastritis with intestinal metaplasia (CAG+IM),19 cases of atypical hyperplasia(Dys),15 cases of early GC and 45 cases of advanced GC were collected.All the tissues were fixed in 10% neutral formalin and embedded in paraffin.2. SP immunostaining technique was used to examine the expression of leptin and MMP-2 in 19 cases of NGM, 19 cases of CAG+IM, 19 cases of Dys, 15 cases of early GC and 45 cases of advanced GC.3. The data were analysized by software SPSS 10.0, chi-square test or Spearmancorrelation was used to compare difference between groups.α=0.05 was considered as statistically significant value.Result:1. The positive staining of leptin protein was mainly located in cytoplasm. There was a significantly much higher positive rate(84.4%) of leptin protein in advanced GC than that in NGM, CAG + IM, Dys and early GC tissues(21.1%,36.8%,47.4%,53.3%;P<0.05 respectively). The positive rate of leptin was 89.3%(25/28) in the group with serosa infiltration and significantly higher than that in the group without serosa infiltration 65.6% (21/32) (P<0.05). The positive rate of leptin was 88.2%(30/34) in the group with lymph node metastasis and higher than that in the group without lymph node metastasis 61.5%(16/26)(P<0.05).Leptin also closely correlated with TNM stages.The positive rate of leptin in III and IV stages was higher than that in I and II stages(90.9%,30/33Vs 59.3% ,16/27,P<0.01). No correlation was found between the leptin expression and histologic grade (P >0.05). 2. The positive staining of MMP-2 protein was mainly located in cytoplasm. Therewas a significantly much higher positive rate(80.0%) of MMP-2 protein in advanced GC than that in NGM, CAG + IM, Dys and early GC tissues (5.3%, 21.1%,36.8%,53.3%,P<0.05respectively). There was a significant difference between NGM and early GC tissues(.P<0.01). The positive rate of MMP-2 was 89.3%(25/28) in the group with serosa infiltration and significantly higher than that in the group without serosa infiltration 59.4%(19/32)(P<0. 01). The positive rate of MMP-2 was 85.3%(29/34) in the group with lymph node metastasis and higher than that in the group without lymph node metastasis 57.7%(15/26) (P<0. 05). MMP-2 also closely correlated with TNM stages.The positive rate of leptin in III and IV stages was higher than that in I and II stages (87.9%, 29/33 Vs 55.6%,15/27,P<0. 01). No correlation was found between the MMP-2 expression and histologic grade (P >0.05).3. There were 36 cases in the GC group where the expression of leptin and MMP-2was positive simultaneously.The simultaneously negative was 6 cases. Spearman correlation showed that leptin had a positive correlation with VEGF in GC(r_s=0.663,P<0.01).Conclusion:1. The increasing tendency for the expression of leptin protein are common incarcinogenesis of gastric. The overexpression of leptin was correlated with infiltration depth, TNM stages and wether there was lymph node metastasis, which suggest that leptin is involve in the process of carcinogenesis, development and metastasis of GC.2. The increasing tendency for the expression of MMP-2 protein are common incarcinogenesis of gastric. The overexpression of MMP-2 was correlated with infiltration depth, TNM stages and wether there was lymph node metastasis. The overexpression of MMP-2 might participate in the process of gastric carcinogenesis and the progression of GC as well as the enhancement of the tumor invasive ability. 3. The expression of leptin protein was positively correlated with the expression of MMP-2 protein in GC.It is indicated that there is a certain regulation between leptin and MMP-2 and they may cooperatively participate in the carcinogenesis, development and metastasis of GC.4. Leptin protein and MMP-2 protein correlate with the carcinogenesis, development, invasion and metastasis of GC, it suggest that leptin and MMP-2 can be used as parameters during the process of malignance and judging prognosis.