| Background and Objectives: The carcinogenesis and development of gastric carcinoma is multistage and a complicated process concerned of many ingredients. The inactivation of anti-oncogenes is important in this process. PTEN is the first tumor suppressor gene possessing the activation of phosphatase enzyme. It not only adjust the growth and proliferation of normal cell, but also inhibit the tumor occurrence, progression and metastasis. The prevenient researches found, the PTEN gene mutation and/or deletions are common in human tumors, but exist lots of differences in digestive tumors. the PTEN gene mutation rates are different in diversified tumors, which indicates the complicacy between PTEN and the tumor occurrence, development. It doesn't lucubrate of the role of the PTEN gene and its protein in carcinogenesis and development of gastric carcinoma. Extracellular signal-regulated kinase approach is an important cellular signal transduction pathway, which transfers extracellular stimulations to cellular nucleus. participating in cellular growth ,proliferation and differentiation, and playing an important role in malignant transformation of normal cell and the tumor occurrence and development. Up to now, the studies found PTEN can down-regulate many cellular signal transduction pathway, but the correlation between PTEN and extracellular signal-regulated kinase approach has been rarely reported. Animmunohistochemistry P-V method was used to detect the expression of PTEN and ERK2 proteins in different pathological lesions of gastric mucosa. To study their roles in carcinogenesis> development and metastasis of gastric carcinoma and the significance of clinicopathology, provide new theoretical foundation for forecasting the early diagnosis, prevention and clinical treatment, judging prognosis of gastric carcinoma.Materials and Methods: (1)58 cases of surgically resected gastric cancer(GC) tissue samples, 81 cases of various gastric changes tissue specimens underwent endoscopy were collected(20 chronic superficial gastritis ^ 26 chronic atrophic gastritis with intestinal metaplasia ^ 35 dysplasia). All the tissues were fixed in 10% neutral formalin and embedden in paraffin. None of the patients had received neoadjuvant chemotherapy or radiation therapy before surgery, They were all confirmed pathololgically. (2) P-V immunohistochemistry technique was used to detect the expression of PTEN and ERK2 proteins in chronic superficial gastritis(CSG)^ chronic atrophic gastritis with intestinal metaplasia (CAG+IM)^ dysplasia (Dys) and gastric carcinoma (GC) tissues. Staining results were evaluated by semi-quantity analysis, which associated with staining intensity and the number of positive cells.(3) The data was analysized by statistical software SPSS10.0, JC2-test , Fisher's exact test and spearman correlation were used to compare the difference between groups, a =0.05 was considered as statistically significant valueResults: (1) The positive staining of PTEN is mainly located in cytoplasm and/or nucleus. There was strongly positive staining in CSG tissues. There was also moderately positive staining in CAG+IM and Dys tissues. However, there was lightly positive staining in GC tissues. The positive rates of PTEN protein were 100%, 92.3%, 71.4% and 46.6% in chronic superficial gastritis> chronic atrophic gastritis with intestinal metaplasia ^ dysplasia and gastric carcinoma, respectively, There were significant differences(p<0.05) when gastric carcinoma group compared with dysplasia group. There were also significant differences (p<0.05) when they compared with chronic superficial gastritis and chronic atrophic gastritis with intestinal metaplasia (p<0.05),separately. There were no significant differences (p>0.05) when chronic superficial gastritis group compared with chronic atrophic gastritis with intestinal metaplasia. The positive rates of PTEN were 44.9% and 75.0% in early gastric carcinoma and advanced gastric carcinoma, There were significant differences when they were compared with each other. In the group with lymph node metastasis and the group without lymph node metastasis, the positive rates of PTEN were 34.4% and 57.7%, respectively. There were significant differences (p<0.05). There were also significant differences in the well and moderately-differentiated group and poor-differentiated group (p<0.05).(2) The positive staining of ERK2 is also located in cytoplasm and/or nucleus. There was strongly positive staining in body of gland cells of GC tissues. There was also moderately positive staining in CAG+IM and Dys tissues. However, there was lightly positive staining in CSG tissues. The positive rates of ERK2 protein were5%N 34.6% ^ 62.9% and 82.8% in chronic superficial gastritis^ chronic atrophic gastritis with intestinal metaplasia> dysplasia and gastric carcinoma, respectively, It presents with progressive tendency for the expression of ERK2. There were significant differences when they were compared with each other(p<0.05). The positive rates of ERK2 were 66.7% and 37.5% in early gastric carcinoma and advanced gastric carcinoma, There were significant differences when they were compared with each other. In the group with lymph node metastasis and the group without lymph node metastasis, the positive rates of ERK2 were 96.9% and 65.4%, respectively. There were also significant differences(p<0.05), The positive rates of ERK2 were 60.0% and 75.8% in the well and moderately -differentiated group and poor-differentiated group, There were no significant differences when they were compared with each other(3) Of 58 cases gastric carcinoma, The positive rates of ERK2 expression in PTEN-negative group were significantly higher than that of PTEN- positive. A significant negative relationship was observed between the expression of PTEN and ERK2 ip <0.05).Conclusions: (1) The reducing tendency for the expression of PTEN are commonin carcinogenesis of gastric cancer. And expression level of PTEN was related to histological differentiation > lymphnode metastasis and tumor stages. Which suggest that PTEN involved in the process of carcinogenesis and development of gastric carcinoma.(2) Expression of ERK2 was moderately increased in CAG+IM and DYS tissues, and significantly increased in GC, which suggest that ERK2 may play a role in the early stage of human gastric carcinogenesis. Expression level of ERK2 was related to lymphnode metastasis and tumor stages, Expression of ERK2 was related to carcinogenesis, development and metastasis of gastric carcinoma.(3) A significant negative relationship was observed between the expression of PTEN and ERK2.Indicating that there was a certain regulation between PTEN and ERK2.They contributed to the carcinogenesis and development gastric carcinoma in coordination.(4) Reduced expression of PTEN protein and progressive tendency for the expression of ERK2 are common in carcinogenesis and progression of gastric cancer. The decrease or deletion of PTEN protein expression may not be able to effectively inhibit the over-activation of ERK signaling pathway, which will result in carcinogenesis, infiltrate and metastasis. So PTEN and ERK2 can be used as parameters in judging the carcinogenesis, development and metastasis of gastric carcinoma, and provide referential foundation for the prevention and prognosis judgement of gastric carcinoma. |
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