Expression And Significance Of Leptin And Leptin Receptor In Gastric Carcinoma

Background and objective:Gastric carcinoma(GC) is one of the most common mailignant neoplasms, and hds 8.6percentage of incidence of mailignant neoplasms in the world. The development ofGC is a course of many genes and steps, with high death rate, which threatenspeoples' life and health seriously and is one of the .mailignant neoplasms researchedweightly in our country. The beginning of GC is secreately, with little syndrome andlow diagnosis in early stage. Studies for many years showed that the mainreason fordeath in patients with GC is metastasis of tumor. The main measure to increase thesurvival rate of GC patients is to study the mechanisms of invasion and metastasis,improve the diagnosis in early stage, which is also the hot and difficult point in GCresearch.Studies showed that leptin and leptin receptors existed in human stomach mucousmembrane tissue, epithelium and GC cells. Leptin can inhibit death of tumor cell,improve its proliferation, increase the invasion to floor membrance and promote thecreaction of vascular, which may be relevant to occurance and development with GC.In our research, immunohistochemical SP(Streptavidin peroxidase) method was usedto examine the expression of leptin and leptin receptor at different stages of gastricdisease, so as to discuss their effects in the beginning, invasion and metastasis of GC, and provide new theory for early diagnosis, clinical treatment and prognosis.Materials and methods:1. 19 cases of normal gastric mucosa(NGM), 19 cases of chronic atrophic gastritiswith intestinal metaplasia (CAG+IM), 18 cases of atypical hyperplasia(Dys), 15cases of early GC and 45 cases of advanced GC were collected. All the tissueswere fixed in 10％neutral formalin and embedded in paraffin.2. SP immunostaining technique was used to examine the expression of leptin andleptin receptor in NGM, CAG+IM, Dys, early GC and 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 wasconsidered as statistically significant value.Result:1. The result of leptin expression:(1)The positive staining of leptin was mainlylocated in cytoplasm. (2) There was a significantly much higher positiverate(80.0％)of leptin protein in advanced GC than that in NGM, CAG+IM, Dysand early GC tissues(15.8％, 31.6％, 44.4％, 53.3％; P＜0.05 respectively). Thepositive rate in early GC group was also higher than that in NGM, CAG+IM andDys (P＜0.05 respectively). (3) The positive rates of leptin in group with well,moderate and poor differentiation were respectively 78.3％(18/23), 70.6％(12/17),70.0％(14/20), with no statistic significance (P＞0.05). The positive rate of leptinwas 89.7％(26/29) in the group with serosa infiltration and significantly higherthan that in the group without serosa infiltration (58.1％, 18/31, P＜0.01). Thepositive rate of leptin was 85.3％(29/34) in the group with lymph node metastasisand higher than that in the group without lymph node metastasis (57.7％, 15/26,P＜0.05).Leptin also closely correlated with TNM stages.The positive rate of leptininⅢandⅣstages was higher than that inⅠandⅡstages(87.9％, 29/33 Vs55.6％, 15/27, P＜0.05).No correlation was found between the leptin expressionand patients' ages and sex.2. The result of leptin receptor expression: (1) The positive staining of leptin receptor was mainly located in cytoplasm. (2) The positive rates of leptinreceptor in NGM, CAG+IM, Dys, early GC and advanced GC were47.4％(9/19), 52.6％(10/19), 55.6％(10/18), 53.3％(8/15), 62.2％(28/45)respectively, with the development of GC, the positive rate of leptin receptorvaried unobviously.(P＞0.05).(3) No correlation was found between the leptinreceptor expression and patients' ages, sex, histologic grade, serosa infiltration,lymph node metastasis and TNM stages.4. The correlation between leptin and leptin receptor expression in GC: There were24 cases in the GC group where the expression of both leptin and leptin receptorwas positive simultaneously. The simultaneously negative was 4 cases.Spearman correlation showed that leptin had no correlation with leptin receptorin GC (r_s=-0.005, P＞0.05).3. The correlation between leptin expression and VEGF expression in GC:Therewere 35 cases in the GC group where the expression of leptin and VEGF waspositive simultaneously.The simultaneously negative was 12 cases. Spearmancorrelation showed that leptin had a positive correlation with VEGF inGC(r_s=0.673, P＜0.01).Conclusion:1. The increasing tendency for the expression of leptin protein are shown incarcinogenesis of gastric. The overexpression of leptin was correlated withinfiltration depth, TNM stages and wether there was lymph node metastasis. Theoverexpression of leptin might participate in the process of gastric carcinogenesisand the invasion and metastasis of GC.2. There was no relationship between the positive expression of leptin receptor andthe development of GC, histologic grade,infiltration depth, TNM stages andwether there was lymph node metastasis.Leptin had no correlation with leptinreceptor in GC. It is indicated that leptin participates in the process of gastriccarcinogenesis and the progression of GC not via up-regulating leptin receptor.