CLINICAL SIGNIFICANCES OF THE EXPRESSION OF METALLOTHIONEIN IN FIVE TYPES EPITHELIUM CELL CANCER

Objective： To study the expressions of （CSC）, bladder transitional cell cancer metallothionein and the significances in cervical squamous cell cancer （BTC）, esophageal squamous cell cancer （ESC）, gastral tubular adenocarcinoma （GC） and large intestinal tubular adenocarcinoma （LIC）. Methods： lmmunohistochemical method was used to examine the expression rates of MT in five types of cancer tissue. Results： The expression rates of MT were 75.00% （24/32） in ESC, 52.27% （46/88） in GTC, 59.46% （44/74） in LIC, 64.86% （48/74） in BTC and 58.57% （41/70） in CSC respectively. The positive rates of MT expression were higher in low differentiation and deep muscular group than those in medium or high differentiation and superficial muscular invasion group （P〈0.05）. Conclusion： The expression of MT is related to differentiation degree and invasion degree.     

胃癌组织中Ets-1的表达及其与血管生成临床病理特征和预后的关系

Objective To investigate the expression of Ets-I in gastric carcinoma,pars-cancerous tissue and metastatic lymph nodes,and to determine the relationship between Ets-1 expression and clinicopathological features,angiogenesis and survival of patients with gastric carcinoma.Methods Gastric carcinoma tissue microarray was used to determine Ets-I protein expression by SP immunohistochemical staining in 189 advanced gastric cancer,54 papacancerous tissues,41 metastatic lymph nodes and 32 control tissues.Results The positive rates for Ets-1 expression of the carcinoma,paracancerous and control tissues were 71.4 %,29.6% and 18.8%,respectively,with a significant difference among the three groups(P ＜0.01).In the cancer tissues,the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis(P ＜0.01),but not associated with degree of differentiation,Lauren's histological type,sex,age,and size of tumor(P ＞0.05).The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different(P ＜0.05).In metastatic lymph nodes,the positive rate for Ets-1 expression was higher.The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors,with a significant difference(P ＜ 0.05).Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P ＜0.05).Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma.Conclusion A higher expression of Ets-1 is involved in carcinogenesis,development,invasion,and metastasis of gastric cancer.Ets-1 plays an important role in angiogenesis in gastric cancer.Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma,though it is not an independent prognostic indicator.     

Expression of Hpa and CD222 in bladder carcinoma and analysis of clinico-pathologic correlation

Objective： Our study aimed to investigate the relationships between the clinico-pathologic features and the heparanase （Hpa） and CD222 expressions in bladder carcinoma. Methods： The expressions of Hpa and CD222 in 95 bladder carcinoma specimens and 20 paraneoplastic bladder tissues （controls） were assessed using the immunohistochemical stain- ing method. Results： The positive expression rates of Hpa and CD222 in bladder carcinoma were 68.42% and 61.05%, respectively. The positive rate of Hpa was significantly higher in the carcinoma specimens than in the control specimens （P 〈 0.01）. Similarly, the Hpa expression in the invasive bladder carcinoma was significantly higher than that in the non-invasive bladder carcinoma （P 〈 0.01）. A positive correlation was observed between the expressions of Hpa and CD222 （P 〈 0.05）. The expressions of Hpa and CD222 were significantly correlated with lymphatic invasion and TNM staging （P 〈 0.05）. The 5-year survival rate was significantly higher in negative expression of the Hpa group than that in the positive expression group （P 〈 0.05）. Compared with the non-co-positive expression group, the 5-year survival rate in the co-positive expression of Hpa and CD222 group was significantly lower （P 〈 0.05）. Conclusion： High Hpa and CD222 expressions in tumor tissues were associated with the occurrence and development of bladder carcinoma. Our results provide helpful information for the further diagnosis and therapy of bladder carcinoma.     

Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas.METHODS The immunohistochemical SP method was used to detect the expression of Coxsaekie and Adenovirus receptor in 48 cases of renalcell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue.RESULTS The positive rates of CAR were 100% in 12 cases of para-tumcr normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P＜0.05). The grades of the tumor were as follows: 22 in Grade Ⅰ, 17in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%,23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P＜0.05). In addition, the number of the cases in stages Ⅰ to ⅣV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P＜0.05).CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.     

Analysis of the Relationship between Expressions of TF and MMP-9 and Prognosis of Breast Cancer Patients

OBJECTIVE To investigate expression of the tissue factor (TF)and matrix metalloproteinase-9(MMP-9)in breast cancers, and to assess their expression in relation to possible prognostic significance. METHODS The expression of TF and MMP-9 in 71 breast cancer specimens were determined by EnVision immunohistochemistry, and the positive expressions related to the patient clinical outcome. RESULTS Positive rates of TF and MMP-9 staining were respectively 43.7%and 42.3%.K-M monofactorial analysis showed that the 5-year survival rate of the patients with a positive expression of TF and MMP-9 was lower than those with negative expression(P<0.05).However,the COX multifactorial analysis indicated that TNM staging and lymph node metastasis were the prognostic factors for breast cancer patients,and that TF and MMP-9 could not be used as the independent prognostic factors(P >0.05). CONCLUSION The positive rates of TF and MMP-9 were considerably high in breast cancers,which could provide useful information for patient prognosis.     

Expression of TGF-β1 and the mechanism of invasiveness and metastasis induced by TGF-β1 in breast cancer

Objective To investigate the expression of MMP-2,TIMP-2,TGF-β1 and TGF-βRI and the relationship among them in breast cancer.Methods The protein expression of MMP-2,TIMP-2,TGF-β1 and TGF-β1R1 was detected on tissue chips by S-P immunohistochemical staining in 160 cases of breast carcinoma.Results The positive rates of TGF-β1,TGF-β1 mRNA,MMP-2,MMP-9,TIMP-1 and TIMP-2 expression were 73.7%,56.2%,96.9%,95.0%,87.5% and 89.4%,respectively.Axillary lymph node metastasis and TNM staging(P ＜0.01 and P ＜0.01,respectively)were positively correlated to the expression of TGF-β1.Relase-free survival of TGF-β1 positive group was lower than that of TGF-β1 negative group(P = 0.023).The expression of M MP-2 or M M P-9 was positively correlated to that of TGF-β1 (r=0.170,P＜0.05;r =0.221,P＜0.01)and was negatively correlated to that of TGF-β1 mRNA(r =-0.126,P ＞0.05;r = 0.019,P ＞ 0.05).Conclusion The expression of TGF-β1 may be closely correlated with the invasion and metastasis of breast cancer.TGF-β1-induced invasiveness and metastasis of breast cancer cells are mediated by MMP-2 and MMP-9.     

P53、C-erbB-2和VEGF在非小细胞肺癌中的表达及其临床意义

Objective: To investigate the expressions and the clinical significance of P53, C-erbB-2 and vascular endothelial growth factor(VEGF)in non-small cell lung cancer(NSCLC).Methods: 121 specimens of NSCLC were examined for P53, C-erbB-2 and VEGF by immunohistochemical staining.Results: The positive rates of P53, C-erbB-2 and VEGF in the carcinomatous tissue were 43%, 39% and 31% respectively.P53 gene protein expression in lung cancer was significantly related to histological type and P-TNM staging of lung cancer patients(P＜0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and cell differentiation(P＞0.05).C-erbB-2 gene protein expression in lung cancer was closely related to histological type and cell differentiation(P＜0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and P-TNM staging of lung cancer patients(P＞0.05).VEGF in lung cancer was only closely related to cell differentiation(P＜0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis, histological type and P-TNM staging of lung cancer patients(P＞0.05).Conclusion: It is possible for P53, C-erbB-2 and VEGF to play an important role in the oncogenesis and development of non-small cell lung cancer.     

EXPRESSION OF c-erbB-2, p53, p16 IN SQUAMOUS CELL CARCINOMA OF ANTERIOR TONGUE IN CHINA POPULATION

Objective: Aberrant expression of c-erbB-2, p53, p16 has been found in oral squamous cell carcinoma. We therefore examined expression of these proteins in squamous cell carcinoma of the anterior tongue and compared their relationship with clinical stages and prognosis. Methods: Seventy-six patients with squamous cell carcinoma of the anterior tongue never treated before were obtained from Cancer Hospital, CAMS. Archive tissues of carcinoma and paracarcinoma were examined for c-erbB-2, p53 and p16 expression by immunohistochemistry.Results: The rates of immunopositive staining of c-erbB-2, p53 and p16 were 64.5%, 61.8% and 23.7% respectively; the positive rates in paracarcinoma mucosa were 19.7%, 22.6% and 55.3% respectively. Overexpression of c-erbB-2 was significantly correlated with short overall survival, metastasis and staging. Overexpression of paracarcinoma p53 was significantly correlated with local recurrence.Conclusion. c-erbB-2 may be used as a prognosis marker for the patients with squamous cell carcinoma of the anterior tongue and p53 as a recurrence marker.     

HER-2和MMP-2在膀胱移行上皮癌组织中的表达及意义

目的：探讨膀胱移行细胞癌（bladder transitional cell carcinoma,BTCC）组织中HER-2和MMP-2蛋白的表达、相关性及意义。方法：应用免疫组织化学链酶卵白素-过氧化物酶复合物（SP）方法,检测82例BTCC组织标本中HER-2和MMP-2蛋白的表达,并与10例正常膀胱组织进行对照研究。结果：82例BTCC组织中,HER-2蛋白的阳性表达率为51.2%,MMP-2阳性率70.7%;正常膀胱组织中未见HER-2和MMP-2蛋白阳性表达。HER-2和MMP-2蛋白的阳性表达随着BTCC的病理分级和临床分期的增高而增加（P〈0.05）;HER-2和MMP-2两者在BTCC组织的表达存在正相关（P〈0.05）。结论：HER-2与MMP-2在膀胱移行上皮癌组织中高表达,两者的表达密切相关,与促进癌浸润和转移有关,可能提示预后较差。     

精子相关抗原9在膀胱移行细胞癌中的表达及临床意义

目的： 探讨精子相关抗原9 (sperm-associated antigen 9,SPAG9)在膀胱移行细胞癌 (bladder transitional cell carcinoma, BTCC)中的表达并分析其临床意义。方法：选取经临床病理诊断的BTCC标本98例,正常膀胱组织30例,应用免疫组化染色方法检测SPAG9在BTCC中的表达和分布情况,分析其与肿瘤的临床分期、病理分级及2年复发率的关系。结果：SPAG9在正常膀胱组织中为阴性表达,而在BTCC组中的阳性表达率为75.5% (74/98),并且随着肿瘤分期和分级的升高SPAG9蛋白的表达增加,SPAG9阳性表达率在病理分级G1、G2与G3级之间的差异有统计学意义 (P<0.05);在临床分期Ta与T1组间的差异有统计学意义 (P<0.05); SPAG9蛋白表达阳性的非肌层浸润性膀胱癌患者,其2年复发率显著高于阴性表达者 (P<0.05)。结论：SPAG9蛋白在BTCC中呈高表达状态,可成为BTCC有意义的肿瘤标志物,并有可能作为判断 BTCC侵袭力、监测复发的重要指标。阻断SPAG9表达有望成为膀胱癌靶向治疗的新靶点。     

P33ING1、p53在膀胱移行细胞癌中的表达及与细胞凋亡的相关性

目的：探讨抑癌基因P33ING1在膀胱移行细胞癌（BTCC）中的表达及其与p53蛋白表达及细胞凋亡的相关性。方法：利用免疫组化S-P法和TUNEL法检测83例BTCC及11例正常膀胱黏膜组织P33ING1、p53的表达及细胞凋亡指数（AI）。结果：83例膀胱移行细胞癌组织中,P33ING1蛋白的阳性表达率为59.03%,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90.9%。P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级有相关性。Spearman相关分析表明P33ING1蛋白表达与p53蛋白表达正相关（P〈0.05）。AI与P33ING1及p53蛋白表达无相关性。结论：P33ING1在膀胱移行细胞癌中表达下降可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53的状态和P33ING1表达水平,对于膀胱癌的诊断、治疗和预后判断可能具有积极意义。     

膀胱尿路上皮癌组织中窖蛋白1的表达及其与患者预后的关系

目的 明确膀胱尿路上皮癌组织中窖蛋白1的表达水平,并探讨其与膀胱尿路上皮癌预后的关系.方法 应用免疫组化法检测85例膀胱尿路上皮癌组织中窖蛋白1的表达,比较其中64例初发者和21例复发者的表达差异,以及窖蛋白阳性和阴性表达初发患者的预后.结果 85例膀胱尿路上皮癌组织中,窖蛋白1表达阳性34例(40.0%).窖蛋白1在初发性和复发性膀胱尿路上皮癌组织中的表达阳性率分别为32.8%和61.9%,差异有统计学意义(P<0.05).21例窖蛋白1阳性表达的初发性膀胱尿路上皮癌患者平均无瘤生存时间为14.2个月,43例窖蛋白1阴性的初发性膀胱尿路上皮癌患者平均无瘤生存时间为18.9个月,两组差异有统计学意义(P<0.05),窖蛋白1阳性表达组的术后无瘤生存率低于阴性表达组(P<0.05).结论 窖蛋白1与膀胱尿路上皮癌的发生有关,其阳件表达是膀胱尿路上皮癌复发的高危因素.     

EZH2 和PTEN在膀胱癌的表达及预后分析

目的:研究膀胱癌组织EZH2 和PTEN基因的表达,探讨其与膀胱癌临床病理特征及无瘤生存的关系。方法:制作80例膀胱移行细胞癌和10例正常膀胱黏膜（对照组）组织芯片,应用免疫组织化学方法检测EZH 2 和PTEN蛋白的表达,采用Kaplan-Meier 单因素和Cox 比例风险模型多因素分析其与膀胱癌无瘤生存的关系。结果:膀胱癌组织中EZH 2 和PTEN阳性表达率分别为80.0% 和45.0% 。EZH 2 和PTEN的阳性表达率在膀胱癌不同临床分期及病理分级组间存在显著性差异（P<0.05）,且两者的表达呈负相关（P=0.033）。 全组膀胱癌患者术后平均无瘤生存期为39.4 个月,1、3、5 年无瘤生存率分别为70.0% 、55.2% 、41.4% 。单因素分析表明:病理分级、肿瘤数目和EZH 2 表达为影响膀胱癌预后的相关因素;多因素分析表明:病理分级、肿瘤数目和EZH 2 表达是膀胱癌复发的独立危险因素。结论:EZH 2 和PTEN异常表达与膀胱癌的发生、发展关系密切。病理分级、肿瘤数目和EZH 2 是膀胱癌预后的独立危险因素。      

COX-2与VEGF在膀胱尿路上皮癌中的表达及相互关系

目的：研究二型环氧化物酶（COX-2）、血管内皮细胞生长因子（VEGF）在膀胱尿路上皮癌中的表达,探讨它们之间的相互关系及与膀胱癌病理分级的关系和临床意义。方法：应用免疫组化方法检测COX-2、VEGF在68例膀胱尿路上皮癌及13例膀胱正常粘膜中的表达,分析它们的表达情况与膀胱尿路上皮癌病理分级及是否浸润的关系、以及各指标之间的相互关系。结果：COX-2与VEGF在膀胱尿路上皮癌中均表达,COX-2的表达随着膀胱癌病理分级的上升而呈上升趋势（P〈0．05）,且两者之间存在明显的正相关性。结论：COX-2与VEGF在膀胱癌中均高表达,在其发生发展中起重要作用,有望为膀胱癌的靶向治疗提供新的途径。     

PTEN与FHIT在膀胱移行细胞癌中的表达及其临床意义

目的：探讨PTEN与FHIT在膀胱移行细胞癌（bladder transitional cell carcinoma,BTCC）组织中的表达及其临床意义。方法：应用免疫组化技术（SP法）检测62例膀胱移行细胞癌和13例正常膀胱黏膜标本中PTEN与FHIT蛋白的表达情况。结果：PTEN、FHIT蛋白在BTCC表达率分别为56.5%和51.6%,明显低于二者在正常膀胱黏膜中的表达,差异有统计学意义（P〈0.05）;在BTCC中PTEN与FHIT蛋白表达均与肿瘤病理分级和分期密切相关（P〈0.05）,在BTCC标本中PTEN蛋白表达与FHIT蛋白表达呈正相关（r=0.448,P〈0.05）。结论：PTEN、FHIT在BTCC的发生、发展中发挥了重要作用。PTEN、FHIT联合检测可作为预测BTCC生物学行为和预后判断的重要指标。     

凋亡相关蛋白Fas及caspase-3在膀胱移行细胞癌中表达及临床意义

目的：探讨凋亡相关蛋白Fas及caspase-3在膀胱移行细胞癌中的表达及其临床意义。方法：应用SP免疫组织化学法检测45例膀胱移行细胞癌及10例正常膀胱黏膜组织石蜡切片中Fas和caspase-3表达的情况，并结合临床资料进行分析。结果：Fas在膀胱移行细胞癌标本中的表达阳性率为46．7％（21／45），而在正常对照组中阳性表达率为100％；caspase-3在膀胱移行细胞癌标本中的表达阳性率为37．8％（17／45），与对照组阳性率为90％（9／10）相比差异有统计学意义（P〈0．05）。Fas的表达与膀胱移行细胞癌的组织学分级，初发和复发及肿瘤数目之间差异有统计学意义（P〈0．05），但与临床病理分期无关；Caspase-3的表达与膀胱移行细胞癌的初发和复发相关（P〈0．05），但与组织学分级，肿瘤数目，临床分期均无关。相关性分析表明，膀胱移行细胞癌中Fas的表达与caspase-3表达呈正相关。结论：Fas在膀胱癌组织中选择性表达降低且与膀胱移行细胞癌的分化程度密切相关的，caspase-3蛋白在膀胱移行细胞癌中表达下降，因此Fas及caspase-3蛋白对于判断膀胱移行细胞癌预后有重要临床指导意义。     

Matriptase和HAI-1在膀胱移行细胞癌中的表达及其意义

目的 检测 Matriptase 及HAI-1在膀胱移行细胞癌(BTCC)中的表达,探讨与BTCC临床病理参数间的关系及其临床意义.方法 在同一组织标本两个石蜡切片中应用免疫组化技术检测Matriptase及HAI-1在BTCC及正常膀胱组织中的表达,并结合临床病理资料分析.结果 Matriptase及HAI-1在BTCC及正常膀胱组织中均有表达;两者在BTCC中的表达阳性率均明显低于正常膀胱组织,组间差异有统计学意义(P<0.05);HAI-1表达与肿瘤病理分级、临床分期呈负相关(相关系数r分别为-0.634,P<0.001;-0.521,P<0.001).Matriptase表达随病理分级升高而降低,中、低分化组明显低于高分化组,差异有统计学意义(P<0.05);在不同临床分期组间差异无统计学意义(P>0.05).Matriptase和HAI-1在正常膀胱组织中表达相关系数r<0.772(P<0.001);在BTCC中r<0.546(P<0.001).结论 Matriptase和HAI-1在BTCC中表达降低,其异常表达在BTCC的发生发展过程中可能具有重要作用,HAI-1可作为判断BTCC恶性程度及预后的新型生物学标记,Matriptase在BTCC中的表达与促分化有关,可能是一种分化程度的指标.Matriptase和HAI-1在BTCC中相关性降低,两者比例失衡可能在BTCC发生发展过程中具有重要作用.     

膀胱尿路上皮癌组织中窖蛋白1的表达及其与患者预后的关系

目的 明确膀胱尿路上皮癌组织中窖蛋白1的表达水平,并探讨其与膀胱尿路上皮癌预后的关系.方法 应用免疫组化法检测85例膀胱尿路上皮癌组织中窖蛋白1的表达,比较其中64例初发者和21例复发者的表达差异,以及窖蛋白阳性和阴性表达初发患者的预后.结果 85例膀胱尿路上皮癌组织中,窖蛋白1表达阳性34例(40.0%).窖蛋白1在初发性和复发性膀胱尿路上皮癌组织中的表达阳性率分别为32.8%和61.9%,差异有统计学意义(P<0.05).21例窖蛋白1阳性表达的初发性膀胱尿路上皮癌患者平均无瘤生存时间为14.2个月,43例窖蛋白1阴性的初发性膀胱尿路上皮癌患者平均无瘤生存时间为18.9个月,两组差异有统计学意义(P<0.05),窖蛋白1阳性表达组的术后无瘤生存率低于阴性表达组(P<0.05).结论 窖蛋白1与膀胱尿路上皮癌的发生有关,其阳件表达是膀胱尿路上皮癌复发的高危因素.