Expression Of Ki67 And HIF-1α In Gastric Cancer And Their Clinical Significance

Objective : To discuss the expression of Ki67 and HIF-1αin gastric cancer organizations and And their relationship with clinical stage , pathological classification , lymph node metastasis of gastic carcinoma . Methods:80 cases of gastric cancer tissue which are surgically resected by the 2nd hospital of Jilin University from January of 2005 to March of 2007 were collected and pathologically confirmed. The tissues are divide as follows : 16 cases of early gastric cancer, 64 cases of advanced gastric cancer by the depth of invasion; 20 cases of high-differentiation , 26 cases of mid- differentiation,34 cases of low- differentiation or not differentiated by the degree of histological differentiation;16 cases of stageⅠ,22 cases of stageⅡ,26 cases of stageⅢ,16 cases of stageⅣ,divided by TNM staging of gastric cancer in 1997; 43 cases without lymph node metastasis, 37 cases with lymph node metastasis, divided by with or without lymph node metastasis.All tissues are fixed by 10% formalin and paraffin-embedded, with 4μm thick serial sections and immunohistochemistry staining. HIF-1α(hypoxia-inducible factor) protein is positive if the cytoplasm or nucleus are brown granules. In five vision which are randomly selected under microscope, 200 cells in each vision .Total1000.The percentage of positive cells were calculated in each slice, no positive cells were negative (-); If positive cells in the vision are less than 10% ,it is the weakly positive (+);Ranging from 10% to 50% is for the moderately positive (+ +);More than 50% is positive (+++).Ki67 positive nuclei were stained brown granules, ki67 labeling index calculation is the same with HIF-1α. The criteria of MVD (Micro vascular density):brown vascular endothelial cells or cells cluster in gastric cancer tissues represent a separate microvascular. As Weidner's ways :select high-density areas in low light microscope, calculate the number of blood vessels which is in three visions and stained brown by CD34 under high microscope vision. The average is the MVD value of the case. The result will be expressed by the average with addition and subtraction of Standard deviation. All the data and results were recorded with Excel and analyzed by statistical software package SPSS11.5 . Count data were tested using chi-square tests. T-test were used to compare the average. Multi-grades comparison were done using Spearman rank correlation analysis.Results:①The expression rate of Ki67 in 80 cases of gastric cancer is 90.00%.Expression degree of Ki67 in different stages of gastric cancer has significant difference (χ~2=19.37, P=0.000). The positive expression rate of ki67 rises with the rising of Clinico - pathologicstaging of gastric cancer. The positive expression rate of Phase III + IV(95.23%) was significantly higher than I and II (85.71%). The difference was significant (P <0.05). There is a correlation between expression degree of hi67 and gastric cancer pathologic staging(r=0.491, P<0.05).②The positive rate of HIF-1αin 80 cases of gastric cancer is 76.25%.The positive expression rate of HIF-1αrises with the rising of Clinico - pathologic staging of gastric cancer. The positive expression rate of Phase III + IV(80.95%) was significantly higher than I and II (55.26%). The difference was significant (P <0.05). There is a correlation between expression degree of HIF-1αand gastric cancer pathologic staging(r=0.284,P<0.05).③Expression rate of Ki67 with lymph node metastasis in gastric cancer was higher than expression rate of negative patients with lymph node metastasis (χ~2=6.90,P=0.009). Lymph node metastasis and expression of Ki67 expression was positively correlated(r= 0.294,P=0.002). Expression rate of HIF-1αwith lymph node metastasis in gastric cancer was higher than expression rate of negative patients with lymph node metastasis (χ~2=9.54,P=0.02). Lymph node metastasis was positively correlated with the expression of HIF-1α(r=0.345,P=0.002).④Blood vessel density of Low-density undifferentiated gastric cancer is higer than the Blood vessel density of mid-highdifferentiated gastric cancer. It has significant difference (t=10.29,P=0.000). ki67 index in PhaseⅢ+Ⅳis higher than PhaseⅠ+Ⅱ. The difference was significant (t=12.88,P=0.000). ki67 index OF patient with lymph node metastasis in gastric cancer is higher than ki67 index of patient without Metastasis (t=10.48,P=0.000)。⑤The correlation of HIF-1αand ki67 is analyzed by Spearman rank correlation . There is a correlation between expression of HIF-1αand ki67 in gastric cancer organizations. (r =0.439,P < 0.01)。Conclusion : The positive expression rate of HIF-1αin this experiment is 76.25%. It is significantly higher than normal tissues . There is no correlation between HIF-1αand the patient's age, sex , tumor location. But There is correlation between HIF-1αand degree of differentiation, the clinical staging and lymph node status. Ki67 index is correlated with the clinical staging and lymph node status . HIF-1αand The expression of ki67 also positively correlated . HIF-1αprotein expression is related with proliferative activity of gastric cancer cell . Generation of Vascular plays an important role in development and Transfer Of malignant tumor . MVD in gastric cancer organization was significantly higher than normal organization in the stomach and increased with Decline Of the degree of differentiation of gastric cancer. Ki67 show a positive correlation with the MVD, probably due to tumor angiogenesis,increase blood supply and oxygen supply , thereby promoting the proliferation of the tumor . The positive expression of HIF-1αin gastric cancer tissues was significantly higher. And it was closely related with clinical staging and lymph node metastases which represented badness degree and clinical pathological factors After healing .