The Relationship between the Expression of p27^(Kip1),p53 and the Infiltration,Metastasis and Prognosis in Gastric Carcinoma

Objective: To study the relationship between the expression of p27Kip1 and p53, and the infiltration, metastasis and prognosis in gastric carcinoma. Methods: The expression of p27Kip1 and p53 at protein level was determined by immunohistochemical assay (two-step method) in 100 cases of gastric carcinoma. Results: Of the 100 cases, the positive rate of p27Kip1 and p53 expressions were 44% and 49%, respectively. In the group of gastric carcinomas with deep infiltration (infiltration group), lymph nodes metastasis group (metastasis group) and death-within-5-years group (death group), the expression of p27Kip1 was statistically lower (_P<0.05). In the metastasis group and death group, the expression of p53 was significantly higher (P<0.05). The results of the monovariate analysis revealed that the 5-year survival rate of the high p27Kip1 expression group was 70.59%, which is higher than those of the low p27Kip1 expression group (54.55%) and the negative experession group (26%). The 5-year survival rate of the high p53 expression group was 19.23%, which was lower than those of the p53 low expression group (43.75%) and the negative group (53.19%). Cox multivariate analysis showed that p27Kip1, like p53, was an independent prognostic index. But p27Klpl protein expression was a stronger independent survival predictor (RR=3.06) than p53 expression (RR=2.33). Conclusion: The low expression of p27Kip1 and the high expression of p53 reflected the more frequent invasion and metastasis, which resulted in the reduced survival of patients. As an independent markers of the gastric carcinoma, the expression of p27Kip1 is more useful than that of p53 in the prognosis prediction of gastric carcinoma.

Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma

AIM： TO investigate the significance of S phase kinase- associated protein 2 （Skp2） expression in human gastric carcinoma and the relation between expressions of Skp2, p27 and PTEN. METHODS： Immunohistochemical analysis was performed on 138 gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, 10 chronic superficial gastritis specimens and 5 normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma specimens for p27 and PTEN expression. RESULTS： Skp2 labeling frequency was significantly higher in intestinal rnetaplasia （12.68±0.86） and adjacent rnucosa （19.324±1.22） than in normal gastric rnucosa （0.53±0.13） and chronic superficial gastritis （0.47±0.19） （P = 0.000）, in dysplasia （16.74±0.82）than in intestinal metaplasia （P = 0.000）; in gastric primary carcinoma （31.34±2.17） than in dysplasia and adjacent rnucosa （P = 0.000）, in metastasis gastric carcinoma in lymph nodes （39.76±2.00） than in primary gastric carcinoma （P = 0.037）, respectively. Skp2 labeling frequency was positively associated with differentiation degree （rho = 0.315, P = 0.000）, vessel invasion （rho = 0.303, P = 0.000） and lymph node metastasis （rho = 0.254, P = 0.000） of gastric cancer. Expression of Skp2 was negatively associated with p27 （rho = -0.451, P = 0.000） and PTEN （rho = -0.480, P = 0.000） expression in gastric carcinoma, p27 expression was positively associated with PTEN expression in gastric carcinoma （rho = 0.642, P = 0.000）.CONCLUSION： Skp2 overexpression may be involvedin carcinogenesis and progression of human gastric carcinoma in vivo, possibly via p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating Skp2 expression.

Expression and significance of KAI1/CD82 and p27 in gastric carcinoma

Objective:To study the expression and significance of KAI1/CD82, p27 proteins in gastric carcinoma.Methods: The expressions of KAI1/CD82, p27 proteins were detected by immunohistchemistry S-P method in 58 cases of gastric carcinoma tissues and 23 normal gastric tissues.Results: The positive rates of KAI1/CD82 and p27 proteins in gastric carcinoma tissues were 29.3% and 34.4%, but 90% and 85% respectively in normal gastric tissue. And there is a significant difference between the two groups. The expression level of KAI1/CD82 and p27 proteins was significantly related to tumor invasive depth, grade of tumor differentiation, the clinical stage and lymph node metastasis, And has nothing to do with age or gender. There was a positive correlation between the expression of KAI1/CD82 and P27 in gastric cancer tissues.Conclusion: The expression of KAI1/CD82 and p27 protein may be involved in the initiation and development in gastric carcinoma, and the combined detection of KAI1/CD82 and p27 proteins may be significant in predicting the invision and metastasis of gastric carcinoma.

SIGNIFICANCE OF Skp2 EXPRESSION IN HUMAN GASTRIC CARCINOMA AND THE RELATIONSHIP BETWEEN Skp2, p27 AND PTEN EXPRESSION

Objective： S-phase kinase-associated protein 2 （Skp2） is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis. In this study, we investigated significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression. Methods： Immunohistochemical analysis was performed on 138 surgical resected primary gastric carcinoma specimens, 102 paired metastasis carcinoma tissue specimens in lymph node from the same set of 138 surgical resected primary gastric carcinoma specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, and 20 normal gastric mucosa specimens for Skp2 and performed on the same set of 138 surgical resected primary gastric carcinoma specimens for p27 and PTEN. Results： Skp2 labeling frequency % was increased dramatically in intestinal metaplasia, dysplasia, and primary gastric carcinoma compared with normal gastric mucosa （P=0.000, all the same）. Skp2 labeling frequency % in metastasis gastric carcinoma in lymph node was significantly higher than primary gastric carcinoma （P=0.037）. Skp2 labeling frequency % was positively associated with differentiated degree （rho=0.315, P=0.000）, vessel invasion （rho=0.303, P=0.000） and lymph node metastasis （rho=0.254, P=0.000） respectively. An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in gastric carcinoma （rho=-0.451, P=0.000） and with its putative negative regulator, the PTEN tumor suppressor protein （rho=-0.480, P=0.000）. p27 expression had positive relationship with PTEN expression in gastric carcinoma （rho=0.642, P=0.000）. Conclusion： Skp2 overexpression is correlated with carcinogenesis and progression of gastric carcinoma： elevated Skp2 expression is correlated with decreased p27 and PTEN in gastric carcinoma, and p27 expression is parallel with PTEN expression. These suggest that PTEN may regulate expression of p27 through the Skp2 pathway, and the effects of Skp2, p27 and PTEN together play an important role in carcinogenesis and progression of gastric carcinoma.

幽门螺杆菌感染与胃癌中p21和p27表达的关系

探讨胃癌中p21^(WAF1)和p27^(KIP1)的表达及其临床意义,并分析幽门螺杆菌(Hp)感染和p21^(WAF1)、p27^(KIP1)表达的关系。采用免疫组化法检测了89例胃癌组织中p21^(WAF1)和p27^(KIP1)表达水平,并采用快速尿素酶试验和组织病理学检测两种方法检查这些胃癌病例的Hp感染情况。实验结果显示,胃癌组织p21^(WAF1)的表达水平在不同病例组织中有所差异。结合临床病理学指数分析显示,降低的p21^(WAF1)表达与较深的肿瘤侵袭密切相关(P<0.05)。免疫组织化学结果显示,p27^(KIP1)无论在细胞浆中还是细胞核内都有表达,p27^(KIP1)核表达水平与胃癌的组织病理学分型密切相关(P<0.05)。此外,还发现Hp阳性病例的p27^(KIP1)阳性表达率明显低于Hp阴性者(P<0.05),而p21^(WAF1)表达阳性率在Hp阳性和阴性胃癌病例中无显著差异(P>0.05)。结果提示,胃癌的进展与细胞周期调节蛋白p21^(WAF1)和p27^(KIP1)的表达下调有关,Hp感染的致癌过程中可能有p27^(KIP1)参与。

西妥昔单抗对胃癌细胞增殖和凋亡的影响

目的观察西妥昔单抗对体外培养的人胃癌细胞株SGC-7901增殖和凋亡的影响。方法不同浓度西妥昔单抗（12．5、25．0、50．0、100．0mg／L）作用于对数期生长的胃癌细胞SGC-7901，噻唑蓝（MTF）法观察生长抑制作用；流式细胞术（FCM）检测对细胞周期和细胞凋亡的影响；逆转录一聚合酶链反应（RT-PCR）法检测半胱氨酰天冬氨酸特异性蛋白酶-3（Caspase-3）mRNA的表达水平；免疫组织化学（SP）法测定细胞内B淋巴细胞／白血病-2（bcl-2）、p-27蛋白表达变化。结果MTr法显示随西妥昔单抗浓度增加，抑制率由（9．76±1．41）％上升至（78．12±3．88）％，并呈现时间依赖性（P〈0．05），FCM结果示G。／G．期细胞比例上升，S期细胞比例下降，呈浓度依赖性（P〈0．05），凋亡率与西妥昔单抗浓度呈正相关。RT-PCR法和SP法结果显示，细胞中Caspase-3、p-27mRNA和蛋白随西妥昔单抗浓度增加而表达增加，bcl-2mRNA和蛋白则表达下降（P〈0．05）。结论西妥昔单抗可抑制体外培养的人胃癌细胞SGC-7901增殖，诱导细胞凋亡，其机制可能与上调Caspase-3、P-27基因转录和蛋白表达，下调bcl-2基因转录和蛋白表达有关。