The Significance of CXCR4 Expression for the Prediction of Lymph Node Metastasis in Breast Cancer Patients

OBJECTIVE The chemokine receptor(CXCR4)CXC chemokine receptor 4)plays an important role in cancer metastasis.We therefore studied differential expression of the CXCR4,as well as that of the biomarker HER2,so as to evaluate whether these biomarkers can be used to predict axillary lymph node metastasis in breast cancer patients. METHODS Immunohistochemistry was used to evaluate the CXCR4 and HER2 expressions and to examine the paraffin sections of the breast cancers at various stages.Positive lymph node expression was found in 80 of the cases,and in 7 there was negative expression. RESULTS Compared to the cases with negative lymph nodes, there was a high expression of CXCR4(26.3% vs.14.3%,P=0.013), and an over-expression of HER2(28.8% vs.14.3%,P=0.011). Moreover,there was a direct correlation between the CXCR4 and HER2 expressions and the tumor staging(P=0.000)and lymph node metastasis(P=0.032).When the two biomarkers,i.e.CXCR4 and HER2,were concurrently labeled,a high expression of one of the biomarkers could be seen in the cases with positive lymph nodes(51.3% vs.28.6%,P<0.003). CONCLUSION The chemokine receptor,CXCR4,is a new-type biomarker in predicting axillary lymph-node metastasis in breast cancers.Compared with the other markers,such as HER2 etc., assessment of CXCR4 can improve the prediction of the presence and extent of lymph node involvement.     

5758例女性乳腺癌激素受体状态及其相关因素分析

Objective To analyze the characteristics of hormone receptor status in Chinese females with breast cancer.Methods The clinicopathalogieal data of 5758 female breast cancer patients surgically treated in our breast caneer center from Jan.1997 to Oct.2008 were retrospectively analyzed.Results The positive rates of estrogen receptor(ER)and progesterone receptor(PR)were 64.1% and 70.2%,repeetively.The ER positive rate was significantly higher in elderly,post-menopausal females with a smaller tumor and well-differentiated histology(P ＜ 0.05),while the PR positive rate was significantly correlated with only histological differentiation and tumor size(P ＜ 0.05).The ER and PR positive rates were significantly higher in the patients with lymph node metastasis than that in those without(P ＜0.05).Multivariate analysis showed that the histological differentiation,T stage,N stage and menopause status were significantly correlated with ER positive rate,while histological differentiation,T stage and N stage were significantly correlated with PR positive rate.Conclusion Our results show that the ER positive rate of breast cancer in Chinese women is lower than that in western high incidence areas.The ER positive rate is signifieandy correlated with age,histological differentiation,tumor size,and menopause status.The PR positive rate is correlated only with histological differentiation and tumor size.Interestingly,the ER and PR positive rates are significantly higher in the patients with axillary lymph node metastases than that in those without.However,further study is needed to verify this special phenomenon.     

NF-κB and MMP-2 expression regulated by Lrig1 through the MEK-ERK signaling pathway in Hazaks' esophageal squamous cell carcinoma北大核心CSCD

Objective: This work aimed to investigate the expression levels of Lrig1, NF-κB, and MMP-2 in Hazak's esophageal squamous cell carcinoma (ESCC), as well as to explore the relationship of Lrig1 expression through the PI3K-AKT and MEK-ERK signaling pathways with clinicopathological indices. Methods: First, RT-PCR analysis was performed to study the expression levels of Lrig1, NF-κB, and MMP-2 in 48 ESCC and noncancerous specimens. Second, some key genes of the PI3K and MEK signaling pathways such as PI3K, AKT1, MEK1, MEK2, MEK5, ERK1, and ERK2 were detected in Lrig1-positive and -negative tissues to identify the possible signaling pathway of Lrig1-regulated NF-κB and MMP-2 expression. Results: The expression of NF-κB (P<0.001, P=0.014) and MMP-2 (P=0.003, P=0.045) was significantly correlated with Lrig1 in cancer and distal normal tissues. Lrig1 may be negatively correlated with NF-κB and MMP-2 at the protein level. MEK5 (P<0.001) and ERK2 (P=0.009) expression was associated with Lrig1 in cancer tissues. PI3K expression was correlated with Lrig1 in the distal normal tissues (P<0.001). The coordinate expression ratio of Lrig1 to NF-κB and MMP2 reached 52.1% (25/48). This co-expression may be related to lymph node metastasis (P=0.020) but not to other clinicopathological features. Conclusions: These findings suggest that MMP-2 and NF-κB expression is related to Lrig1 in Hazak's ESCC, and that MEK and ERK2 mRNA expression are related to Lrig1. The co-expression of NF-κB, MMP-2, and Lrig1 may promote lymph node metastasis in ESCC among Hazak people. Lrig1 may regulate the expression of target genes not through the PI3K-AKT pathway but through the MEK-ERK signaling pathway. Further related studies are needed in the future.     

核转录因子-κB在胰腺癌中的表达及其与上皮细胞间质转化的关系

 Objective　To investigate the expression of NF-κB and epithelial-mesenchymal transition(EMT) related markers E-cadherin and Vimentin proteins in human pancreatic cancer tissues and its relation with the malignant features． Methods　The expression of NF-κB、E-cadherin and Vimentin proteins in 62 cases of pancreatic cancer tissues were detected by using immunohistochemistry and compared with the clinicopathological data of pancreatic cancer. Results　The positive expression rate of NF-κB was 81 ％ (50/62), Vimentin protein increased of expression was 61 ％ (38/62), and E-cadherin protein loss of expression was 55 ％ (34/62) in pancreatic cancer. The positive expression rate of NF-κB was significantly related with the lymph node metastasis (χ2=11.761, P ＜0.05), distant metastasis(χ2＝9.225, P ＜0.05), the absent expression of epithelial marker E-cadherin protein (r =0．352, P <0．05) and the positive expression of mesenchymal marker Vimentin protein (r =0．343, P <0．05), but there was no relation with the patients gender, age, tumor location, tumor type and tumor differentiation (P ＞0．05)． In addition, the significant correlation of E-cadherin expression loss and Vimentin expression with tumor lymph node metastasis and distant metastasis was found (χ2＝6.914, 4.984, 7.753, 5.144, P <0.05). Conclusion　The overexpression of NF-κB in pancreatic cancer may accelerate invasion and metastasis of pancreatic cancer through inducing EMT．     

Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.     

Clinicopathological Significance of E-cadherin and PCNA Expression in Hunman Non-small Cell Lung Cancer

OBJECTIVE This study was designed to assess E-cadherin (E-cad)and proliferating cell nuclear antigen(PCNA)expression as well as their clinicopathological significance in hunman non- small cell lung cancers(NSCLCs).Possible molecular mechanisms of differentiation and metastasis of NSCLCs are discussed. METHODS Immunohistochemical and immunofluorescence double staining were performed to examine the expression of E-cad and PCNA in 68 primary NSCLCs cases. RESULTS The E-cad expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.E-cad expression had a positive correlation with the histological- differentiated grade.A significant difference of E-cad expression was found between metastatic and non-metastatic groups.PCNA expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.The PCNA expression had a reverse correlation with the histological-differentiated grade.A significant difference of PCNA expression was found between metastatic and non-metastatic groups.The E-cad and PCNA expression presented a reverse correlation. CONCLUSION E-cad expression is not associated with the histological type of NSCLC,but is associated with differentiation and metastasis of the cancer.Down-regulation of E-cad expression affects the proliferation of cancer cells.Conjoint analysis of E-cad and PCNA expression is a good way to evaluate tumor biological behavior.     

Correlations of 99Tcm-HL91 SPECT hypoxia imaging with HIF-1α and VEGF expression in non-small cell lung cancer

Objective 99Tcm-HL91(99Tcm labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime)is a potential noninvasive marker of tumor hypoxia.It has been reported that 99Tcm-HL91 has validity for hypoxia imaging in non-small cell lung cancer(NSCLC).The aim of this study was to evaluate the 99Tcm-HL91 SPECT hypoxia imaging of NSCLC,the expression of inducible hypoxia factor-1α (HIF-1α)and vascular endothelial growth factor(VEGF),and to analyze their correlations with clinicopathological characteristics.Methods Twenty NSCLC patients who underwent radical resection were enrolled into this study prospectively.99Tcm-HL91 SPECT scanning was performed in all patients at one or two days before surgery.After intravenous injection of approximately 740 MBq 99Tcm-HL91,anterior,posterior and lateral planar images were collected at 2,4 and 6 hours,respectively.Regions of interest (ROls)were drawn in the tumor and the contralateral normal lung tissue,and the radioactivity ratio of tumor to normal tissue(T/N)was calculated.Immunohistochemistry was used to detect the expression of HIF-1α and VEGF in sequential histological sections of specimens.Results Among the 20 NSCLC patients,13 showed positive expression of HIF-1α and 15 had positive expression of VEGF,with a positive rate of 65.0% and 75.0%,respectively.The uptake of 99Tcm-HL91 was strongly correlated with the expression status of HIF-1α.No correlation between HIF-1α and VEGF expression levels was observed.The HIF-1α expression level was not correlated with histological subtype,but with lymph node involvement.The expression levels of HIF-1α and VEGF were positively correlated with tumor stage.Conclusion The result of 99Tcm-HL91 SPECT hypoxia imaging is found to be positively correlated with expression of HIF-1α in the non-small cell lung cancer.HIF-1α expression is positively correlated with VEGF expression.Furthermore,both HIF-1α and VEGF expressions are increasing with the increase of tumor stage.     

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features简

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.     

E-钙黏蛋白在鼻咽癌组织中的表达水平及其与颈部淋巴结转移的关系

Objective To investigate the expression of E-cadherin in nasopharyngeal carcinoma ( NPC) and its relationship with cervical lymph node metastasis. Methods The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry. Results Lower expression of E-cadherin was associated with advanced N-stage of the tumor ( P = 0. 018 ). There was no significant correlation between the expression of E-cadherin and lymph node size ( P = 0.435 ). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0. 000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56. 5% ) than that in the patients with bilateral lymph node metastases (32. 6% ) , however, the difference was not significant (P =0. 059). The expression rates of E-cadherin in patients with lymph node metastasis in levels Ⅱ , Ⅲ and Ⅴa were higher than that in levels Ⅰ , Ⅳ, Vb and Ⅵ, but with a non-significant difference (P = 0.059). Conclusion The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i. e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.     

E-钙黏蛋白在鼻咽癌组织中的表达水平及其与颈部淋巴结转移的关系

Objective To investigate the expression of E-cadherin in nasopharyngeal carcinoma ( NPC) and its relationship with cervical lymph node metastasis. Methods The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry. Results Lower expression of E-cadherin was associated with advanced N-stage of the tumor ( P = 0. 018 ). There was no significant correlation between the expression of E-cadherin and lymph node size ( P = 0.435 ). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0. 000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56. 5% ) than that in the patients with bilateral lymph node metastases (32. 6% ) , however, the difference was not significant (P =0. 059). The expression rates of E-cadherin in patients with lymph node metastasis in levels Ⅱ , Ⅲ and Ⅴa were higher than that in levels Ⅰ , Ⅳ, Vb and Ⅵ, but with a non-significant difference (P = 0.059). Conclusion The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i. e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.     

Clinical significance of XRCC1 gene expression in human breast cancer and its cell and molecular mechanisms北大核心CSCD

Objective: To investigate the expression of X-ray repair cross complementing 1 (XRCC1) in human breast cancer and its relationship with the clinical characteristics, and to analyze the effects of XRCC1 over-expression on the proliferation and migration of breast cancer MB-231 cells and the molecular mechanism. Methods: The expression level of XRCC1 mRNA in breast cancer cell lines and human breast cancer tissues was detected by real-time fluorescent quantitative PCR. The expression of XRCC1 protein in human breast cancer tissues was detected by immunohistochemistry. The relationship between the expression of XRCC1 protein and the clinicopathological characteristics of breast cancer patients was analyzed. The pcDNA3.1(+)-Flag-XRCC1 plasmids were transfected into breast cancer MB-231 cells for the overexpression of XRCC 1 gene. Then the proliferation activity was detected by CCK-8 and soft agar plate clone formation assay. The cell cycle and apoptosis were detected by FCM method. The cell migration and invasion were detected by Transwell chamber assay. The expressions of cell cycle-, apoptosis- and migration-related proteins were detected by Western blotting. Results: The expression level of XRCC1 mRNA was significantly decreased in most breast cancer cell lines (all P < 0.001). As compared with the normal mammary epithelium and the paired adjacent breast tissues, the expression levels of XRCC1 mRNA and protein were downregulated in human breast cancer tissues (all P < 0.001). The expression level of XRCC1 mRNA was positively correlated with the prognosis of breast cancer patients (γ 2 =0.052, P =0.046), and XRCC1 protein expression was correlated with tumor diameter, lymph node metastasis, histological grade and TNM stage (all P < 0.05). After the overexpression of XRCC 1 gene, the proliferation, colony formation, invasion and migration of breast cancer MB-231 cells were significantly inhibited (all P < 0.01), the cell cycle was significantly blocked in G1 phase (P < 0.001), and the apoptosis rate was significantly increased (P < 0.001). Furthermore, the expressions of p21, p27, Bax, cleaved caspase-3 and E-cadherin were significantly upregulated (all P < 0.001), while the expressions of cyclin-dependent kinase 4/6 (CDK4/6), cyclin D1, Bcl-2, N-cadherin and vimentin were down-regulated (all P < 0.001) in MB-231 cells with XRCC1 overexpression. Conclusion: XRCC1 expression is down-regulated in breast cancer cell lines and tissues, and its expression level is positively correlated with the prognosis of breast cancer patients. Restoring XRCC 1 gene expression can inhibit cell growth, migration and invasion, and can induce apoptosis. So XRCC1 may be a potential tumor suppressor regulating the occurrence and development of human breast cancer. © 2019 by TUMOR.     

Expression and clinical significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions简

Objective： The aim of our study was to observe the expressions and clinical Significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： Immunhistochemical UltraSensitiveTM S-P method was employed to detect the expression of E-cadherin, β-catenin and E-cadherin-catenins complex in 128 cases of invasive ductal carcinomas, 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia, 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The express of E-cadherin, β-catenin and their relationship with mult biological parameters including histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： （1） The staining patterns character of E-cadherin, β-catenin and E-cadherin-catenins complex： In UDH breast tissues, E-cadherin and a-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The abnormal expression of the three proteins occurred in breast invasive ductal carcinomas, ductal carcinoma in situ and atypical ductal hyperplasia tissues, showing cytoplasmic or nuclear staining, decrease and loss of cytomembrane staining. （2） The abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex in invasive ductal carcinomas were 53.91%, 65.63% and 81.25%, which were significantly higher than that in ductal carcinoma in situ, atypical ductal hyperplasia, usual ductal hyperplasia tissues （P 〈 0.01）. Compared with usual ductal hyperplasia breast tissues group, the abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex were significantly decreased （P 〈 0.01） in the breast cancer group. However, there was no significance of the abnormal expression rate between ductal carcinoma in situ and atypical ductal hyperplasia tissues groups （X2 = 0.76, P = 0.38; x2 = 0.14, P = 0.70; x2 = 0.81, P = 0.37; X2 = 2.19, P = 0.14） （P 〉 0.05）. （3） There was a significantly difference in the mean E-cadherin, β-catenin and E- cadherin-catenins complex frequency between estrogen receptor ＆ progesterone receptor positive IDC group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was no difference in the mean E-cadherin, β-catenin and E-cadherin-catenins complex frequency between age （_〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm） （P 〉 0.05）. Conclusion： In breast cancer, the expressions of E-cadherin, β-catenin and E-cadherin-catenins complex are abnormally decreased and are correlated with pathology grade, differentiation disturbance and metastasis. E- cadherin and β-catenin may be as the predictors for prognosis. Combined detection may improve accuracy and sensitivity of predicting metastasis and prognosis of breast Cancer.     

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast,and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast(ADH and Peri-PM with ADH),50 specimens of breast in situ ductal carcinomas(DCIS),and 50 specimens of invasive ductal carcinomas(IDC).Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that:the differences among the 4 groups(normal breast tissues,breast premalignant lesions,DCIS and IDC,P<0.05)were significant, and there were also statistically significant differences between any 2 groups(P<0.05)except for the β-tubulin positive expression comparing DCIS versus IDC(P>0.05).In addition,β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH(P<0.05).Following the degree of breast epithelial hyperplasia involved,and its development into carcinoma,the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis(P<0.05),but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression.Studies of aberrations of centrosomal proteins provide a new way to explore the mechanism of breast tumorigenesis.     

Prognostic Value of P-gp and p27 in Patients with Esophageal Squamous Cell Carcinoma

Objective： To evaluate the prognostic value of P-gp and p27 expression in patients with esophageal squamous cell carcinoma （ESC）. Methods： The expressions of P-gp and p27 were detected by immunohistochemistry in 104 cases of ESC, and the clinicopathological characteristics were analyzed as well. Results： The positive rate of P-gp expression in 104 cases of ESCs was 32.7%. The positive rate of P-gp expression in the group that survived over 3 years （17.5%） was significantly lower than that in the group died within 3 years （53.3%） （x^2=14.227, P〈0.001）. The positive rate of p27 expression in 104 cases of ESCs was 67.3%. The positive rate of p27 expression in the group that survived over 3 years （75.8%） was significantly higher than that in the group died within 3 years （56.5%） （x^2=4.361, P〈0.05）. The patients with poorer differentiation whole wall invasion, lymph node metastasis and more advanced TNM stage had a shorter survival than did those with better differentiation, more superficial invasion, no lymph node involvement and earlier TNM stage; and it was statistically significant （P〈0.05）. However, tumor size, macropathologic type, age and gender had no prognostic impact on ESC patients （P〉0.05）. Conclusion： P-gp and p27 expression levels had a clinical prognostic significance in ESC. It could provide a reference basis for selecting the chemotherapy projection. The tumor differentiation degree, depth of invasion, lymph node involvement and TNM stages all were correlated to ESC patients＇ survival.     

HRCT Scans of Peripheral Non-Small Cell Lung Cancers and their Relationship with Cyclin D1 Expression： a Longitudinal Study

OBJECTIVE To investigate cyclin D1 expression in peripheral lung cancers and its relationship with CT signs and prognosis. METHODS Cyclin D1 expression in peripheral lung cancers and its relationship with the CT imaging and prognosis were analyzed retrospectively by means of SP immunohistochemistry and spiral CT scanning in 92 patients with peripheral lung cancer verified by pathology. RESULTS Cyclin D1 expression was related to deep lobulation,spiculate protuberance,short thin spinules sign and mediastina lymph node metastasis.Cyclin D1 expression was not related to tumor size,cavity,pleural indentation,histological type,differentiation,tumor TNM stage,age or sex.Cyclin D1 was a negative prognostic factor whose over-expression indicated a poor prognosis. CONCLUSION Cyclin D1 expression may play an important role in the occurrence,progress and CT scan results of lung cancers.Cyclin D1 was a negative factor whose over-expression implied a poor prognosis.Detection of the cyclin D1 and observation of the CT scan can be considered as indexes of clinical diagnosis and prognostic evaluation.     

RhoA和核因子κB在胃癌中的表达及其临床意义

目的 探讨RhoA和核因子κB(NF-κB)在胃癌组织中的表达,分析其与胃癌患者临床病理特征及预后的关系.方法 利用免疫组化、组织芯片技术检测189例胃癌、54例相应癌旁及32例正常胃黏膜组织中RhoA蛋白和NF-κB蛋白的表达.用Kaplan-Meier法行单因素生存分析,应用Cox回归模型进行多因素生存分析.结果 RhoA蛋白在胃癌、癌旁和正常胃黏膜组织中的表达阳性率分别是84.7%、68.5%和65.6%,胃癌与癌旁及正常胃黏膜组织的阳性率差异有统计学意义(P＜0.05).NF-κB蛋白在胃癌、癌旁和正常胃黏膜组织中的表达阳性率分别是75.1%、42.6%和15.6%,且三者的阳性率相互比较,差异均有统计学意义(P＜0.05).RhoA和NF-κB在胃癌组织中的蛋白表达呈正相关(r=0.203,P=0.005).RhoA的蛋白表达与胃癌的浸润深度有关(P＜0.05).NF-κB的蛋白表达与胃癌的浸润深度和有无淋巴结转移有关(P＜0.05).单因素分析结果显示,肿瘤大小、有无淋巴结转移、浸润深度和NF-κB的蛋白表达影响胃癌患者术后的生存(P＜0.05);多因素回归分析结果显示,NF-κB蛋白表达、有无淋巴结转移和浸润深度为影响胃癌患者预后的独立因素(均P＜0.05).结论 RhoA和NF-κB参与胃癌的发生、发展,并在胃癌的浸润和转移中起重要作用;NF-κB的蛋白表达水平、有无淋巴结转移和浸润深度是影响胃癌患者预后的独立因素.

Abstract：

Objective To investigate the expression of RhoA and NF-κB in gastric carcinoma and their correlation with clinicopathological fearures.To determine the effective prognostic factors of long-term suivival of gastric carcinoma patients.Methods The role of RhoA and NF-κB in gastric carcinoma was assessed by tissue array technology and the levels of RhoA and NF-κB expression in paraffin-embedded tissues was quantified by immunohistochemistry from 189 cases of gastric carcinoma, 54 cases of their adjacent tissues, and 32 cases of normal gastric mucosa.The prognosis of gastric carcinoma was evaluated by Kaplan-Meier survival analysis and Cox multivariate regression analysis.Results The positive rates of RhoA expression were 84.7%, 68.5% and 65.6% in gastric carcinoma, adjacent tissues and normal mucosa, respectively.The expression of RhoA in gasric carcinoma was significantly higher than that in adjacent tissues and normal mucosa ( P ＜ 0.05 ).The positive rates of NF-κB expression were 75.1%,42.6% and 15.6%% in gastric carcinoma, adjacent tissues and normal mucosa, respectively.The expression of NF-κB in gasric carcinoma was significantly higher than that in adjacent tissues and normal mucosa (P ＜ 0.05 ).RhoA was positively linked with NF-κB ( r = 0.203, P = 0.005 ).In gastric carcinoma, the expression of RhoA was related with depth of invasion (P ＜ 0.05), and the expression of NF-κB was related with depth of invasion and lymph node metastasis ( P ＜ 0.05 ).The Kaplan-Meier survival analysis showed that the tumor size, lymph node metastasis, depth of invasion, expression of RhoA and NF-κB can shorten the cumulative survival rate.With these paramaters entering the Cox multivariate regression analysis mode, it was revealed that expression of NF-κB, lymph node metastasis and depth of invasion are independent prognostic factors.Conclusions The overexpression of RhoA and NF-κB is involved in the occurrence and development of gastric carcinoma.RhoA is positively linked with NF-κB.They are correlated with the invasion and metastasis of gastric carcinoma.The expression of NF-κB, lymph node metastasis, depth of invasion are independent prognostic factors playing an important role in prediction of the clinical outcome after radical resection of gastric carcinoma.     

Correlation between Expression of P38 MAPK-Signaling and uPA in Breast Cancer

OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase(p-p38)and uPA and the correlation of their expression with breast cancer clinicopathological characteristics,and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells. METHODS Immunohistochemistry(S-P) was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues.Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells,and uPA expression a er treatment with SB203580,a specific inhibitor of p38 MAPK. RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively.The expression of p-p38 was positively related to the expression of uPA(r=0.316,P<0.05).The expression of p-p38 and uPA was related to lymph node metastas is and the TNM stage(P<0.05),but it was not related to the patient’s age or tumor size(P>0.05).The expression of p-p38 and uPA in MDA-MB-231 cells was higher than that in MCF-7 cells.SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression. CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression,and it may be an important process in breast cancer invasion and metastasis.     

HIF-1α和VEGF-C在乳腺癌淋巴管生成中的作用机制

Objective To investigate the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-C (VEGF-C) and the correlations with clinic parameters, and to make sure the effect of DOI:10.3760/cma.j.issn.1673-422X.2013.10. 基金项目：安徽省卫生厅自然科学基金（09C230）作者单位：241000 安徽省芜湖市第二人民医院乳腺外科（赵迎春、朱永云、罗传瑜）,病理科（李勇）通信作者：赵迎春,E-mail: lcy0508@hotmail.com 联系人: 赵迎春 lcy0508@hotmail.com 电话：05533909558 手机：18155317401 the two genes in the lymphangiogenesis and lymph node metastasis of breast cancer. Methods The expressions of HIF-1α and VEGF-C were investigated by means of immunohistochemistry in samples from 78 cases of breast cancer and 20 cases of breast benign lesions. The density of the lymphatic microvessels immunohistochemically stained by D2-40 antibody was calculated. The relationships between HIF-1α, VEGF-C, LVD and clinicopathological parameters were analyzed statistically. Results HIF-1α expression occurred in 52 out of the 78 tumor samples (66.67%), while VEGF-C expression was observed in 41 out of the 78 tumor samples (52.56%). HIF-1α and VEGF-C expressions in breast cancer were significantly higher than those in beingn disease (15% and 10%; χ²=17.26, P=0.000; χ²=11.71, P=0.001). The expressions of HIF-1α and VEGF-C were significantly correlated with regional lymph nodal involvement (χ²=5.80, P=0.016; χ²=7.26, P=0.007) as well as late TNM classification (χ²=8.51, P=0.004; χ²=6.02, P=0.014), disregarding the patient’s age, tumor diameter, histological grade and pathologic type (P＞0.05). In addition, HIF-1α expression was positively correlated with VEGF-C expression (r=0.254, P=0.025). Higher LVD was found in both high HIF-1α and high VEGF-C expression cases (t=2.19, P=0.017; t=3.25, P=0.001). Conclusion HIF-1α may play a crucial role in the lymphangiogenesis and lymph node metastasis by regulating the expression of VEGF-C in breast cancer. Therefore, HIF-1α may become a particularly promising target for controlling lymph node metastasis in breast cancer.     

EXPRESSION OF E-CADHERIN/CATENIN COMPLEX IN BREAST CANCER

Objective： To detect the expressions of E-cadherin, α-catenin and β-catenin and analyze the relationship between Ecadherin-catenin adhesion complex and clinicopathological features in breast cancer. Methods： The expressions of E-cadherin, α-cadherin and β-catenin in specimens of 54 breast cancer, 21 normal breast tissues around tumor, 15 breast hyperplasia of usual type and 15 breast atypical hyperplasia were detected by immunohistochemical method. Results： In 21 normal breast tissues, E-cadherin and α-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The staining character of the three proteins in breast hyperplasia of usual type was the same as that in normal breast tissue. In breast atypical hyperplasia, the abnormal expression rates of E-cadherin, α-catenin and β-catenin were 6.7%, 13.3% and 26.7%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 33.3%. In breast cancer, the abnormal expression rates of E-cadherin, α＋catenin and β-catenin were 51.9%, 63.0% and 61.1%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 88.9%. Abnormal expression of E-cadherin and α-catenin were significantly correlated with histological grade. Abnormal expressions of α-catenin and β-catenin were significantly correlated with TNM staging, axillary lymph nodes metastasis and postoperative distant metastasis. Abnormal expression of E-cadherin-catenin complex was correlated with TNM staging, histological grade and axillary lymph nodes. Abnormal expression of β-catenin was negatively correlated with expression of HER-2. COX multiple factor analysis showed that E-cadherin or α-catenin or β-catenin was not independent prognostic indicator. Conclusion： Abnormal expressions of E-cadherin, α-catenin and β-catenin frequently occur in breast cancer. Abnormal expression of E-cadherin-catenin complex is correlated with differentiation disturbance and metastasis. Combined measurement of E-caherin, α-catenin and β-catenin may improve accuracy and sensitivity of predicting metastasis and prognosis of breast cancer.