Expression Of Tumor Suppressor Gene PTEN And Survivin In Human Gastric Carcinoma And Its Clinical Significance

Objective To investigate the expression of tumor supresssr gene PTEN and apoptosis inhibitor gene Survivin in human gastric carcinoma and study its clinical-pathological implication and its clinical significance.Methods The expression of PTEN and Survivin were detected by immunohistochemistry SP method in 68 cases of gastric carcinoma, 21 of atypical hyperplasia of gastric mucosa, 33 of adjacent normal gastric mucosa and 46 cases the metastasis lymph nodes. Results:1. Expression of PTEN protein: (1) Positive immunostaining with the antibody was observed in the cytoplasm of tumor cells. (2) 44.1 percent (30 of 68) of cases had expression of PTEN in the tumor cells, and in 74.1% of cases (15 of 21) of the dysplasia, and 100% of cases (33of 33) of the normal mucosa it were present. There was a significant positive correlation between gastric carcinoma specimens and normal mucosa specimens and dysplasia (P<0.05). (3) In 68 cases cancer tissues, compared with without invasion serosal stratum group, the PTEN protein expression in invasion serosal stratum groups decreased significantly (P<0.05). Tumors with lymph node metastases(31.7%) had loss PTEN protein expression than those without metastasis(63.0%) (P<0.05). The PTEN expression between â…  + â…¡ and â…¢+â…£ stage, the difference was significant (51.9% v s 39.0%)(P<0.05).The positive rates of PTEN in high and middle degrees of differentiation were significantly higher than that in low degree of differentiation(52.4% v s 30.8%). The positive rates of PTEN decreased with clinical stage, the poor differentiation, deep invasion and lymph nodes metastasis(P<0.05). PTEN protein expression had no relation to the patients' age, sex, tumor size and location, and clinical-pathological stage (P>0.05).2. Expression of Survivin: (1) Survivin expression was located in both the cytoplasm and the cytoplasmic membrane of the tumor cells, and interstitium was negative. (2) 0% (0/33) normal mucosa, 23.8% (5/21) dysplasia, and 66.2% (45/68) gastric carcinoma specimens showed Survivin positive stained in the cytoplasms. In gastric carcinoma specimens, the intensity of Survivin expression was remarkably increased compared with matched normal mucosa specimens and dysplasia (p<0.05). (3) When Survivin expression was compared with clinicopathological features, in 68cases cancer tissues divided into invasion serosal stratum or without invasion serosal stratum group (55.1%, 16/29)and deep or full stratum group(74.4%, 29/39). The authors found that the deeper the extent of tumor infiltration, the higher the Survivin expression (P<0.05). Tumors with lymph node metastases(78.0%, 32/41) had more Survivin protein than those without metastasis(48.1%, 13/27)(P<0.05). According to clinical-pathological stage, the gastric carcinoma samples were divided into I , II, III,and IV stage. Comprising the Survivin expression between I + II (51.9%,14/27)and III+IV stage(75.6%,31/41), the difference was significant(p<0.05). The positive rates of Survivin increased with clinical stage, deep invasion and lymph nodes metastasis (P<0.05). Besides, the Survivin expression had no relation to the patients' age, sex, tumor size and location, degree of differentiation (P>0.05).3. Expression of PTEN and Survivin protein in the primary and metastasis lymph nodes of gastric carcinoma. The positive rates of PTEN in the primary gastric carcinoma (48.4%, 20/41) was significantly lower than that in the metastasis lymph nodes(28.3%, 13/46) (PO.05) . Compared with the primary gastric carcinomas (65.9%, 27/41), this matched sample demonstrated and markedly increased Survivin immunostaining in the metastasis nodes (82.6%, 38/46) (P<0.05).4. Combined expression of PTEN and Survivin protein in gastric carcinoma: A significant negative relationship was observed between the expression of PTEN and Survivin in gastric carcinoma (r=-0.553, p<0.05). Between the patients with over-expression PTEN protein, and Survivin negative expression and those with over-expression of Survivin and PTEN protein negative expression, the cases of lymph node metastasis and invasion serosal stratum t>f the former were significantly higher those of the latter (p<0.05). Conclusions1. Reducing expression of PTEN protein occurs commonly in gastric carcinoma and correlates with tumor stage, histological poor differentiation and lymph node metastasis. PTEN gene play an important role in the occurrence and development of gastric carcinoma. It is suggested that PTEN can be a useful marker for predicting invasion and met;..stasis ability of gastric carcinoma.2. The abnormal expression of Survivin correlates with the occurrence and development of gastric carcinoma. Survivin was over-expression in gastric carcinoma. Expression of Survivin had a significant relation with the invasion depth, lymph node metastasis, TNM stage. Survivin is an important prognostic indicator of gastric carcinoma.3. PTEN and Survivin gene play synergistic action in the occurrence and development of gastric carcinoma. Combined expression of PTEN and Survivin protein showed a significant association with invasion and metastasis of gastric carcinoma. It implies that the occurrence and development, invasion and metastasis of gastric carcinoma is a procedure involved of multi-gene and multi-procedure.