Study On The Expression Of TGF-β₁,TGFβⅡ And Smad4 Protein In Gastric Mucous Of Patients With Precancerous Leisions And Gastric Cancer

Objective:To investigate both the function of TGF-β1,TGF-βRⅡand Smad4 which belong to TGF-βsignal passway and the relationship among the three protein in the carcinogenesis and development of gastric cancer. We evaluated the expression of TGF-β1,TGF-βRⅡand Smad4 protein in gastric mucous of the patients with gastric cancer or precancerous leisions.Methods:20 patients with intestinal metaplasia(IM),20 patients with dysplasia(Dys),46 patients with gastric cancer(GC) and 20 sex, age-matched health subjects were included in the present study. The diagnosis had been based on the gastric biopsies. According to the pathology report and surgery result, tumor were divided into such subgroups: well differentiation group(22 cases) and poorly differentiation group (24 cases);without regional lymph node invasion group(21 cases) and with regional lymph node invasion group(25 cases);without serosal invasion group (22 cases) and with serous invasion group(24 cases),without distant metastasis group(36 cases) and with distant metastasisgroup(10 cases), stage (TNM)Ⅰ,Ⅱgroup(19 cases) and stage Ⅲ,Ⅳgroup(27 cases).All of the subjects had no other diseases. No GC patients had received chemotherapy or radiation therapy or other adjuvant therapy. 5 specimens(2 from antrum,2 from fundal and 1 from cornu gland region, big enough and fetched muscle)were obtained when they were performed by gastroscopy. All of the specimens were fixed with 10% Formalin and embedded with paraffin. They were cut into 5-μm thick sections. A serial section from each specimen was stained with hematoxylin and eosin (H & E) for histological evaluation. Immunohistochemical staining of the sections for TGF-β1,TGF-βRⅡ and Smad4 protein was performed by using image analysis system to get the result.Results:1. TGF-β1 positive staining was observed in cytoplasm. Nomal epithelium positive cells was fewer and homogeneously stained,whereas in gastric cancerous tissue, more positive tumor cells were heterogeneously distributed and the color was deeper. TGF-βRⅡpositive staining was observed both in cytoplasm and cytomembrane. The positive cells were much more and the stain was also deeper in normal epithelium, while in gastric cancer tissue the positive cells were fewer and even no one is positive. In normal epithelium of the stomach, immunostaining of Smad4 was observed in cytoplasm and simultaneously in nuclei, while there was positive immunostaining for Smad4 only in the cytoplasmin cancer cells and the stain was much weaker even lack of stain. 2.The expression level(positive areas%) of TGF-β1 in GC group was 64.62±14.71 which has a significant difference from NC group(18.97±10.86, P<0.01), IM group(24.42±13.45, P<0.01) and Dys group(33.60±14.61, P<0.01).There was no statistical significance between NC and IM group(p>0.05).The expression of TGF-β1 were much higher in Dys group than that in GC group(p>0.05).There was a significant difference among TGF-βRⅡexpression in GC group(17.91±10.66) and NC group(61.94±12.64, P<0.01),IM group(58.07±11.14, P<0.01) and Dys group(53.35±14.72, P<0.01). We didn't find statistical difference between NC and IM groups(p>0.05),IM and Dys groups(p>0.05). The expression of Smad4 protein in GC group was 23.57±14.31 which has a significant difference from NC group(70.33±12.13, p<0.01),IM group(67.93±13.93, p<0.01) and Dys group(68.82±13.22, p<0.01). We didn't find statistical difference between NC and IM gro ups(p>0.05), IM and Dys groups(p>0.05). 3.In GC group, the expression of TGF-β1 was significantly higher in poorly differentiation(71.29±10.05) than that in well differentiation(57.33±15.70,P<0.01). TGF-βRⅡand Smad4 protein staining in poorly differentiation group(14.09±9.63,16.64±12.81) was lower than that in well differentiation(22.08±10.35,P<0.01；30.22±12.20, P<0.01). With lymph nodeinvasion group, the expression of TGF-β1 was significantly higher(72.30±7.57) than that in without lymph node invasion group(55.47±16.02,P<0.01). TGF-βRⅡ was lower(14.82...