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Objective To detect the expression of EIF5A2 in hepatocellular carcinoma(HCC) and to explore its relation with clinicopathological characters and prognosis of HCC patients. Methods The expression of EIF5A2 mRNA and protein in 12 pairs of fresh HCC and corresponding non-tumor tissues adjacent to the cancer was examined by qRT-PCR and Western blot. The expression level of EIF5A2 in 284 pairs of HCC and adjacent non-tumor tissues was detected by IHC staining. Then we analyzed between EIF5A2 expression and clinical pathological parameters and prognosis of HCC patients. Results The relative expression levels of EIF5A2 mRNA and protein in fresh HCC tissues were significantly higher than those in the corresponding adjacent non-tumor tissues (t=5.305, P=0.0003; t=10.120, P < 0.001); EIF5A2 expression in 284 HCC tissues was significantly higher than that in the corresponding adjacent non-tumor tissues (z=-12.186, P < 0.001). The expression of EIF5A2 was significantly correlated with tumor size (χ2=13.079, P < 0.001), tumor multiplicity (χ2=4.589, P=0.032) and differentiation degree (χ2=4.844, P=0.028). The 3- and 5-year overall survival time and disease-free survival time of the patients with high expression of EIF5A2 were significantly shorter than those with low expression of EIF5A2 (P < 0.001). EIF5A2 was an independent prognostic factor affecting the 3- and 5-year overall survival time and disease-free survival time of HCC patients (P < 0.05). Conclusion The up-regulation of EIF5A2 expression may be related with the occurrence and development of hepatocellular carcinoma. The high expression of EIF5A2 is an independent influence factor for poor prognosis and EIF5A2 can be used as a potential molecular marker for predicting the prognosis of HCC patients.
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Objective@#To examine the expression of ATAD2 in different liver lesions and its clinical significance.@*Methods@#ATAD2 expression in 60 hepatocellular carcinoma (HCC) surgical specimens (49 of which have concurrent liver cirrhosis), 43 HCC biopsy specimens, 2 high-grade liver dysplastic nodule specimens, 3 low-grade liver dysplastic nodule specimens, 50 liver cirrhosis tissue samples, and 20 normal liver tissue samples were measured using immunohistochemistry. The F-test, q-test, t-test, and chi-square test were used for statistical analysis of data.@*Results@#ATAD2 was expressed in 56 HCC surgical specimens (93.33%), 35 HCC biopsy specimens (81.40%), and 2 high-grade liver dysplastic nodule specimens (2/2), but not in the low-grade liver dysplastic nodule, liver cirrhosis tissue, and normal liver tissue samples. The mean expression of ATAD2 was significantly higher in HCC tissues than in high-grade and low-grade liver dysplastic nodule tissues, liver cirrhosis tissue, and normal liver tissue (F = 22.96, q = 3.138, 3.972, 12.272, and 9.101, respectively, all P < 0.01). There were no significant differences in the mean expression and positive expression rate of ATAD2 between HCC surgical and biopsy specimens (t = 1.40, P > 0.05; χ² = 3.47, P >0.05). Of the 35 HCC biopsy specimens that expressed ATAD2, the mean ATAD2 expression was ≥1% in 35 specimens (100%), ≥3% in 27 specimens (77.14%), and ≥5 % in 23 specimens (65.71%). In addition, among the pathological grade I-II HCC biopsy specimens, the mean ATAD2 expression was ≥1% in 28 specimens (100%), ≥3% in 22 specimens (62.86%), and ≥5% in 19 specimens (54.29%). Moreover, ATAD2 expression in HCC was associated with serum alpha-fetoprotein level, presence of hepatitis B virus surface antigen (HBsAg), and presence of concurrent liver cirrhosis (t = 2.09, 2.30, and 2.18, respectively, all P < 0.05).@*Conclusion@#ATAD2 may play an important role in HCC tumorigenesis, and may be involved in malignant transformation of cells. ATAD2 expression can be a valuable marker for differentiating the nature of lesions in liver biopsy tissues during clinical practice.
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<p><b>BACKGROUND</b>Neoadjuvant chemotherapy (NACT) plays an important role in systemic chemotherapy for non-small cell lung cancer (NSCLC). P-glycoprotein (P-gp), lung resistance related protein (LRP), multidrug resistance-associated protein (MRP) and glutathione S-transferase (GST-π) may be associated to drug resisitance to chemotherapy in NSCLC. The aim of this study is to investigate the expressions of P-gp, LRP, MRP and GST-π in samples from NSCLC patients before and after treatment with NACT, and their quantitative changes, so that to evaluate the influence of NACT on drug resistance to chemotherapy of NSCLC.</p><p><b>METHODS</b>Total 92 specimens from 72 cases of NSCLC, including 52 samples of surgery excision from non-NACT-treated patients and 20 paired samples before and after NACT from the same patient, were studied. The expression of P-gp, LRP, MRP and GST-π was detected with tissue chip technique and immunohistochemistry. The quantitative analysis was carried out by computer image analysis system..</p><p><b>RESULTS</b>In the samples before NACT, the positive rate of P-gp, LRP, MRP, GST-π expression was 66.67% (48/72), 72.22% (52/72), 81.94% (59/72), 83.33% (60/72), respectively. The expressive intensity of P-gp, LRP and GST-π was significantly stronger in adenocarcinoma than that in squamous cell carcinoma (P < 0.05, P < 0.001, P < 0.001, respectively); there was no significant difference in the expression of MRP between adenocarcinoma and squamous cell carcinoma (P > 0.05). In samples after treatment with NACT, the expression of P-gp, GST-π demonstrated by average optical density (AOD) and integral optical density (IOD) were significantly higher (P < 0.05, P < 0.001 respectively) than that in biopsied samples taken before NACT; The change in expression of P-gp, GST-π was also showed difference by different histopathological types, differentiations, ages, sizes, clinical stages as well as lymph node metastasis or not (P < 0.05 or P < 0.001). There was no significant difference between samples taken before and after NACT (P > 0.05) in the expression of LRP and MRP demonstrated by both of AOD and IOD.</p><p><b>CONCLUSIONS</b>The results suggest that drug resistance in adenocarcinoma is primarily stronger than that in squamous cell carcinoma. NACT may enhance acquired drug resistance of NSCLC through inducing the expression of drug resistance protein. The results indicate that acquired drug resistance must be considered with the application of NACT to NSCLC patient in clinic, especially to patient in stage I and II. Since NACT may lead to the enhancement of acquired drug resistance in stage I and II, this may dwindle the therapeutic effect of chemotherapy after surgery. Comparative examination of drug resistance proteins before and after NACT, combining with comprehensive consideration of chemical regimens of NACT, should be recommended during chemotherapy of NSCLC for both before and after surgery.</p>
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<p><b>BACKGROUND</b>It is well known that vascular endothelial growth factor (VEGF) and its receptors are closely related to tumor angiogenesis, but the exact relationship with patients' prognosis is unclear till now. The aim of this study is to explore the expression of VEGF and its receptors KDR, Flt1 in pulmonary carcinoma and their relationship with patients' prognosis.</p><p><b>METHODS</b>The expression of VEGF, KDR and Flt1 was examined immunohistochemically by PV-9000 method in 75 cases of pulmonary carcinoma with complete follow-up records.</p><p><b>RESULTS</b>There was an extensive expression of VEGF, KDR and Flt1, mainly in the cytoplasm of tumor cells (TCs), fibroblasts (FBs), and endothelial cells. The distribution of VEGF, KDR and Flt1 was heterogeneous, mainly located at periphery of the tumor mass or necrosis. The positive rate of VEGF, KDR and Flt1 in the TCs was all significantly higher than that in the FBs (P < 0.01, P < 0.02, P < 0.02). Both in TCs and FBs, the positive expression of VEGF, KDR and Flt1 was related to the postoperative survival of patients (P < 0.01, P < 0.01, P < 0.01; P < 0.01, P < 0.01, P < 0.05). The survival time in patients with positive VEGF, KDR or Flt-1 in TCs was significantly lower than that in those with corresponding negative one respectively (P < 0.0001, P < 0.0005, P < 0.0005). There was a positive correlation between VEGF and Flt1 in TCs (P < 0.01), between VEGF in FBs and Flt1 in TCs (P < 0.01), and also between VEGF and KDR or Flt1 in FBs (P < 0.01, P < 0.01).</p><p><b>CONCLUSIONS</b>VEGF may act as a considerable promoting growth factor on tumor cells via Flt1, mainly in autocrine and less in paracrine manner. VEGF, KDR and Flt1 may exert important roles in prognosis of patients with pulmonary carcinoma.</p>
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BACKGROUND: Vascular endothelial growth factor receptor plays an important role in the blood vessel growth and prognosis of many solid tumors. However, there are few reports regarding the relationship between vascular growth factor receptor and prognosis of lung cancer.OBJECTIVE: To probe into the relationship between the expressions of vascular endothelial growth factor receptor F1t1, KDR and the metastasis and prognosis of lung cancer.DESIGN: Single sample study based on pathological samples SETTING: Department of pathology in a university.MATERIALS: Totally 75 lung cancer specimens were randomly selected from the specimens removed by Department of Thoracic Surgery of Qingdao University from January 1985 to December 1990. The study was conducted in the Department of Pathology of Qingdao University from September to November 2002.METHODS: Immunohistochemical method PowerVision TM-9000 (PV-9000)was used to assay the Flt1 and KDR expression in 75 lung cancer specimens.MAIN OUTCOME MEASURES: Expression of vascular endothelial growth factor F1t1 and KDR in lung cancer and its relationship with age, sex,pathological type, histological grading, tumor size, lymph node metastasis and prognosis, as well as the expression of F1t1, KDR in tumor cells and fibroblasts.RESULTS: There is extensive expression of F1t1 and KDR in lung cancer tissues, especially in cytoplasm and cell membrane of tumor cells, also in cytoplasm of fibroblasts and vascular endothelial cells. The positive rates of F1t1 and KDR in tumor cells are much higher than those iu matrix fibroblasts (x2 = 6.07,5.88, P ＜ 0.05). There is no difference in the positive rates of these two receptors in tumor cells and fibroblast between cases with different age, sex, pathological types, pathological grading( P＞0.05). There is significant difference in the positive expression rates of Flt1 and KDR in tumor cells among three groups with different tumor size(x2 = 10. 35, 7.29, P ＜ 0.05)while there is no difference in fibroblasts(x2=2.86,2.56, P ＞ 0. 05). There is also significant difference in positive rates of F1t1 and KDR in tumor cells and fibroblasts between groups with and without lymph node metastasis (x2 =4.72 -9.32, P＜0.05) and among three groups with different survival time(x2 = 8.81 - 19. 19, P ＜ 0. 05) . The expression of Flt1 and KDR in tumor cells has greatly positive correlation( r =0.44, P＜0.01).CONCLUSION: The expression of Flt1 and KDR in tumor cells is much higher than that in matrix fibroblasts which suggests that the growth of lung cancer is mainly dependent on autocrine metabolism. The expressions of these two receptors in tumor cells relate to lymph node metastasis, survival time after operation and cooperate with each other. It suggests that it is of great value to assess the metastasis and prognosis of lung cancer by jointly testing the expression of F1t1 and KDR.