Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.METHODS:Purified gastric adenocarcinoma cells(GAC)and normal gastric epithelial cells(NGEC)were obtained from 15 patients with gastric cancer by laser capture microdissection.All of the peptide specimens were labeled as18O/16O after trypsin digestion.Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry(nanoRPLC-MS/MS).The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis.The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry(IHC).The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.RESULTS:A total of 78 differential proteins were identified.Western blotting revealed that ANXA1 expression was significantly upregulated in GAC(2.17/1,P<0.01).IHC results showed the correlations between ANXA1protein expression and the clinicopathological parameters,including invasive depth(T stage),lymph node metastasis(N stage),distant metastasis(M stage)and tumour-lymph node metastasis stage(P<0.01).However,the correlations between ANXA1 protein expression and the remaining clinicopathological parameters,including sex,age,histological differentiation and the size of tumour were not found(P>0.05).CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis,progression,invasion and metastasis of GAC.This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.

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.

EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D1 gene would be helpful to judge the prognosis of gastric cancer.

Caveolin-1,E-cadherin and β-catenin in Gastric Carcinoma,Precancerous Tissues and Chronic Non-atrophic Gastritis

Objective： To investigate the expressions of caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressions with the development of gastric cancer. Methods： The expressions of caveolin-1, E-cadherin and β-catenin were detected by biotin-streptavidinperoxidase （SP） immunohistochemistry on 58 gastric cancer tissues, 40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues. The correlation between the expressions of caveolin-1, E-cadherin and β-catenin, and the clinicopathologic parameters of gastric cancer was analyzed retrospectively. Results： The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues （P〈0.01）. An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues （P〈0.01）. Moreover, low expressions of caveolin-1, E-cadherin and β-catenin correlated with tumor size, depth of invasion, lymph node metastasis and TNM stage （P〈0.05）. The positive rates of caveolin-1 and E-cadherin expressions decreased （P〈0.01）, while an abnormal rate of β-catenin expression increased inversely, with the degree of atypical hyperplasia （P〈0.01）. Caveolin-1 expression correlated positively with E-cadherin （r=0.41, P〈0.05）. Caveolin-1 （r=-0.36, P〈0.05） and E-cadherin （r=-0.45, P〈0.05） expressions negatively correlated with abnormal β-catenin expression. Conclusion： These results suggested that dysregulated expressions of caveolin-1, E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.

Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion

AIM: To investigate the relation of expression transfor-mation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS: By using immunohistochemistry, expres-sion of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index (Ki-67) were detected and analyzed. RESULTS: In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas (including signet-ring cell carcinomas) was the highest. It was nega-tively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, in-vasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in inva-sive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest (51.5%, 17/33). The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was signifi -cantly higher (92.9%) than in tunica muscularis of in-vasive gastric cancer cases, as well as in patients withlymph node metastasis than in those without lymph node metastasis. CONCLUSION: Up-regulation of claudin-1 expres-sion and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neo-plasms. Further study is needed to elucidate the pre-cise mechanism and the relation of claudin-1 expres-sion with the neoplasm progress.

Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma

AIM: To investigate the expression of CD73 and hypoxia-inducible factor-1α (HIF-1α) in human gastric carcinoma, and explore their clinical significance and prognostic value. METHODS: CD73 and HIF-1α expressions were detected by immunohistochemistry in consecutive sections of tissue samples from 68 gastric carcinoma patients. The peritumor tissues 2 cm away from the tumor were obtained and served as controls. The presence of CD73 and HIF-1α was analyzed by immunohis-tochemistry using the Envision technique. RESULTS: CD73 and HIF-1α expressions in gastric carcinoma were significantly higher than those in gastric mucosal tissues as control (P < 0.001) and showed a close correlation (Spearman r = 0.390, P = 0.001). Overexpression of CD73 was positively correlated with differentiation of tumor (P = 0.000), histopathology (P = 0.041), depth of invasion (P < 0.001), nodal status (P = 0.003), metastasis (P = 0.013), and the American Joint Committee on Cancer (AJCC) stage (P < 0.001). High expression of HIF-1α was positively correlated with tumor diameter (P = 0.031), depth of invasion (P = 0.022), and AJCC stage (P = 0.035). The overall survival rate was low in the patients with high expression of CD73 (P < 0.001). Moreover, CD73+/HIF-1α+ patients had the worst prognosis (P < 0.001). CD73 expression was proven to be an independent predictor for patients with gastric carcinoma by both multivariate Cox regression analysis (P = 0.021) and receiver operating characteristic curves (P = 0.001).CONCLUSION: CD73 expression correlates closely with HIF-1α expression in gastric carcinoma. CD73 could be an independent prognostic indicator for gastric carcinoma.

Expression of KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder （TCCB） and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB （P〈0.05）, but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB （P〉0.05）. The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples （P〈0.05）. Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant （r=0.316, P〈0.05）. It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

AIM: To investigate the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in gastric carcinoma and its clinical significance and to explore its relationship with cell proliferation. METHODS: Expressions of IGFBP-2 and Ki-67 in 118 cases of gastric carcinoma and 40 cases of normal gastric mucosa were detected by EnVision immunohistochemical technique. RESULTS: Expression of IGFBP-2 in gastric carcinoma was higher than that in normal gastric mucosa (P < 0.01). There was no difference between high- and low-grade gastric carcinoma (P > 0.05). Expression of IGFBP-2 in advanced gastric carcinoma was higher than that in early gastric carcinoma (P < 0.05). Expression of IGFBP-2 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.01). IGFBP-2 expression was a positively related to the clinical stage of gastric carcinoma (P < 0.01). There was a positive correlation between IGFBP-2 and Ki-67 (P < 0.05). CONCLUSION: IGFBP-2 may be involved in carcino- genesis and progression of gastric carcinoma by promoting cell proliferation.

TTF-1和P40共表达的非小细胞肺癌2例并文献复习

分析2例共表达甲状腺转录因子1(thyroid transcription factor-1,TTF-1)和蛋白40(protein 40,P40)的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的临床病理学特征。2例患者均为老年男性,均有长期吸烟史,并伴有胸闷、胸痛、咳嗽等呼吸道症状;CT检查提示肺癌;镜下瘤细胞呈巢团状分布,具有类似鳞状上皮分化特征,可观察到细胞边界和细胞间连接,无腺腔结构和黏液。2例细胞角蛋白(cytokeratin,CK)7、TTF-1、CK5/6、P40、P63均呈弥漫强阳性,P53均呈突变型表达模式,无整合酶相互作用分子-1(integrase interactor-1,Ini-1)和染色质重塑复合物核心催化亚基-1(brahma-related gene 1,BRG-1)表达缺失,细胞增殖指数Ki-67增高。2例均发生肿瘤蛋白53(tumor protein 53,TP53)基因突变。同时具有腺上皮和鳞状上皮分化免疫表型的NSCLC极为罕见,迄今为止8篇文献(含本研究在内)共报道的12例共表达TTF-1和P40的NSCLC病例中,10例检测到TP53基因突变。因病例数极少,2021年世界卫生组织胸部肿瘤分类未提出确切的诊断分型和预后建议,仍需要更多的病例报道补充。

KAI-1、Ki-67和HER-2/neu表达在T_(1-3)N_0M_0肾癌术后转移中的意义

背景与目的:随着我国经济水平的提高和国民自我保健意识的增强,体检成为发现肾癌的重要手段,因此早期肾癌的比例上升,但是国内尚缺乏大样本T_(1-3)N_0M_0肾癌术后转移发生率的调查,而且术后转移机制目前尚不明确,有关KAI-1、Ki-67标记指数、HER-2/neu与肾癌迟发性转移关系的研究更少。因此本研究拟探讨KAI1、Ki-67和HER-2/neu表达与T_(1-3)N_0M_0肾癌术后迟发性转移的相关性和临床意义。方法:随访1991—2000年经手术治疗T_(1-3)N_0M_0肾癌患者。以术后转移病例为转移组,未转移者为对照组。应用EnVision二步法以HER-2/neu和Ki-67多克隆抗体、用PowerVision二步法以KAI-1单克隆抗体分别对两组肾癌标本行免疫组织化学染色。采用卡方检验对比两组KAI-1、Ki-67和HER-2/neu表达差异。结果:T_(1-3)N_0M_0肾癌241例术后发现迟发性转移24例(转移组),未转移194例(对照组),失访23例。218例肿瘤KAI-1、HER-2/neu和Ki-67表达率分别是82.6%、27.5%和83.5%。转移组KAI-1表达率(20.8%)和过表达率(4.2%)显著低于对照组的90.2%、73.7%(均P<0.001)。转移组HER-2/neu表达(62.5%)和过表达率(20.8%)均高于对照组的23.2%、0(均P<0.05、0.001)。转移组Ki-67过表达率(54.2%)显著高于对照组的3.6%(P<0.001)。结论:KAI-1、Ki-67和HER-2/neu均与T_(1-3)N_0M_0肾癌术后转移的发生存在相关性。三者均有助于评估肾癌预后。应对KAI-1表达缺失、HER-2/neu和Ki-67过表达的T_(1-3)N_0M_0期肾癌手术后进行密切随访。

KAI-1和CD44v3在喉癌组织中的表达及其相关性研究

目的了解喉癌组织中KAI1和CD44v3表达的情况,探讨其在喉癌中的意义及与淋巴转移的关系。方法采用免疫组织化学(SP)法分别检测40例喉癌患者的咽喉黏膜组织、30例正体检者咽喉黏膜组织中KAIl和CD44v3的表达水平。并分析两者在喉癌不同分化程度、临床分、有无淋巴结转移的癌组织中表达的差异及其相关性。结果癌组织中KAI1的表达低于在正常喉黏膜组织中的表达(x^2=8.86,P<0.01),在癌组织中表达与分化程度、临床分期及是否有淋结转移无关(P>0.05),但阳性表达的强度与临床分期及是否有淋巴结转移有关(P<0.05);CD44v3在癌组织中的表达高于正常咽喉黏膜组织(x^2=18.36,P<0.01),表达与临床分期及是有淋巴结转移有关(P<0.05),与分化程度无关。KAI1及CD44v3在癌组织中的表达具有相性(x^2=4.19,P<0.05),关联系数r=0.67。结论 KAI1的表达可能抑制喉癌的发生及转移程,CD44v3可能促进了喉癌的发生和转移。

KAI1蛋白在人胃癌中的表达及临床意义

目的:通过研究KAI1蛋白在胃癌组织中的表达水平,预测其与胃癌生物学行为的关系,探讨其对胃癌的发生、浸润和转移的作用;通过对胃癌组织KAI1蛋白的表达,评估胃癌浸润和转移的潜能,判断预后,及对胃癌的治疗提供新的思路。方法:免疫组化方法对30例胃癌患者组织及正常胃黏膜组织的KAI1蛋白表达分别进行检测。手术标本病理均证实为胃癌,周围正常组织距离癌组织6cm以上。患者术前均未接受任何抗肿瘤治疗。结果:30例胃癌组织中KAI1蛋白表达阳性6例,占20.0%;正常胃黏膜组织中KAI1蛋白阳性表达28例,占93.3%,两者有显著差异。KAI1蛋白表达与胃癌的病理分化程度、临床分期及淋巴结转移呈负相关(P<0.05)。结论:KAI1蛋白在胃正常黏膜组织中的阳性表达明显高于在胃癌组织中的阳性表达,KAI1蛋白表达与胃癌的病理类型、临床分期、淋巴结转移呈负相关,提示KAI1基因具有抑制胃癌浸润和转移作用。

胃癌中KAI1蛋白表达与临床病理特征的相关性

目的:探讨KAI1蛋白在胃癌中的表达及其与临床病理特征的相关性。方法:应用S-P免疫组化法检测50例胃癌及13例胃良性病变和7例正常胃黏膜组织中KAI1蛋白的表达情况。结果:胃癌组织中KAI1蛋白的表达率为22%,显著低于胃良性病变(84.6%)(P<0.05)及正常胃黏膜组织(100%)(P<0.05)。低、未分化癌的阳性率(12.1%)低于高、中分化癌(41.2%)(P<0.05);随着癌组织浸润程度的进展,KAI1蛋白的阳性率呈降低趋势(T1为66.7%,T2为23.5%,T3为15.0%,T4为0);有淋巴结转移的胃癌组织中KAI1蛋白阳性率(13.2%)低于无淋巴结转移的胃癌组织(50.0%);KAI1蛋白的表达与肿瘤的大小、部位及患者的年龄、性别无关。结论:在胃癌的进展过程中KAI1蛋白表达逐渐降低。KAI1蛋白表达降低在胃癌的浸润、转移过程中起着重要的作用。检测KAI1蛋白可能成为监测胃癌进展及临床上判断其预后的重要参考指标。

KAI1蛋白的表达与胃癌转移关系的研究

目的:探讨KAI1蛋白的表达与胃癌转移的关系。方法:免疫组化方法对10例正常人及51例胃癌患者组织中的KAI1蛋白表达分别进行检测。结果:在正常及胃癌组织中均有不同程度的KAI1蛋白表达,胃癌伴淋巴结转移的KAI1蛋白表达水平明显低于无淋巴结转移者(P<0.01);表达的降低或缺失与肿瘤的组织学分级(P<0.05)和淋巴结转移(P<0.05)明显相关;KAI1蛋白表达阳性者和阴性者的3年生存率分别为82.3%和49.0%,差异有显著性(P<0.05)。结论:KAI1蛋白低表达在胃癌的转移中起一定的作用。

Abnormal DNA-PKcs and Ku 70/80 expression may promote malignant pathological processes in gastric carcinoma

AIM:To determine the expression of the catalytic subunit of DNA-dependent protein kinase(DNA-PKcs)and the Ku70/Ku80 heterodimer(Ku 70/80)in gastric carcinoma.METHODS:Gastric biopsies were obtained from 146gastric carcinoma patients[Helicobacter pylori(H.pylori)-negative:89 and H.pylori-positive:57]and 34from normal subjects(H.pylori-negative:16 and H.pylori-positive:18)via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University.Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system.An‘‘in-house’’rapid urease test and modified Giemsa staining were employed to detect H.pylori infection.The expression of DNA-PKcs and the Ku 70/80protein was detected by immunohistochemistry.RESULTS:Overall,the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer(χ2=133.04,P<0.001 for DNA-PKcs andχ2=13.06,P<0.01 for Ku)compared with normal gastric mucosa.There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa,and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0%(0/34),whereas the rate in gastric cancer(GC)was 93.8%(137/146).The difference between the two groups was statistically significant.Additionally,the positive rate of Ku 70/80 was79.4%(27/34)in normal gastric mucosa and 96.6%(141/146)in gastric cancer.The DNA-PKcs protein level was significantly increased in gastric cancer(MannWhitney U=39.00,P<0.001),compared with normal gastric mucosa.In addition,there was a significant difference in the expression of Ku 70/80(Mann-Whitney U=1117.00,P<0.001)between gastric cancer and normal gastric mucosa.There was also a significant difference in Ku70/80 protein expression between GC patients with and without H.pylori infection(P<0.05).Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression(r=-0.447,P<0.05).Moreover,Ku70/80 expression was negatively correlated with both clinical stage(r=-0.189,P<0.05)and H.pylori colonization(r=-0.168,P<0.05).CONCLUSION:Overall,this research demonstrated that enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma.

Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma

AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma.METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues.CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.

Expression of Bmi-1,P16,and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance

Objective Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. Tlle present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma （UCC）. Methods A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used ill the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed. Results The expression of Bmi-l, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in tlle cervical neoplasia and normal colorectal mucosa （P〈0.05）. The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis （P〈0.01） and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization （P〈0.05）. Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features （P〉0.05）. The Kaplan-Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients （P〈0.05）. A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC （r=0.419, P=0.001）. Conclusions The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-I and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the expression of CD44v6 in UCC patients. The positive expression of p16 protein is possibly associated with the tumorigenesis, but not with the metastasis or prognosis of UCC.

Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication

AIM To clarify the association between aldo-keto reductase family 1 member B10(AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.METHODS In this study,we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response(SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios(HRs) of AKR1B10 expression for hepatocellular carcinoma(HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test.RESULTS Of the 303 chronic hepatitis C patients,153(50.5%) showed scarce hepatic AKR1B10 expression,quantified as 0%,which was similar to the expression in control normal liver tissues. However,the remaining 150 patients(49.5%) exhibited various degrees of AKR1B10 expression in the liver,with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years(range 1.0-10.0 years),8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression(≥ 8%) was an independent risk factor for HCC development(HR = 15.4,95%CI: 1. 8- 1 3 2. 5,P = 0. 0 1 2). T h e 5- y e a r c u m u l a t i v e incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression,respectively(P < 0.001). During the follow-up period after viral eradication,patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression.CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.

The expressions of Pin1, β-catenin and cyclin D1 in elderly lung carcinomas and their significance

Objective： To investigate the expressions and correlations of Pin1, β-catenin and cyclin D1 in elderly lung carcinomas. Methods： The expressions of Pin1, β-catenin and cyclin D1 were examined in the specimens of 92 elderly lung carcinomas and 10 normal lung tissues by immunohistochemistry and explored the relationship between the expression levels and clinicopathological factors. Results： （1） The overexpression of Pin1 and cyclin D1 in lung carcinomas was 46 （50%） cases and 60 （65.22%） cases respectively and 56 （60.82%） cases showed positive immunoreactivity for 13-catenin in the nuclear and （or） cytoplasmic fraction in tumor tissues. In normal tissue, the expressions of Pin1 and cyclin D1 were negative, the expression of β-catenin was lied in cell membrane. （2） In lung carcinomas the expressions of Pin1, β-catenin and cyclin D1 correlated with tumor differentiation （P 〈 0.05）. The pesitive expression rate and intensity of Pin1 correlated with tumor stage （P = 0.032） and lymph node positive disease （P = 0.041）. The expression of β-catenin correlated with lymph node positive disease （P = 0.012）. （3） High expression levels of Pin1 correlated with aberrant I]-catenin expression （P = 0.000） but did not show a correlation with cyclin D1 （P = 0.157）. Conclusion： In elderly lung carcinomas, the positive expression of Pin1 causes abnormal accumulation of β-catenin and actives its target gene, however, this target gene was not cyclin DI. The detection of Pin1 expression had some clinical significance in estimating prognosis of elderly patient with lung carcinomas.

FRAGILE HISTIDINE TRIAD GENE EXPRESSION AND ITS CORRALATION WITH MISMATCH REPAIR PROTEIN IN HUMAN SPORADIC COLORECTAL CARCINOMA

Objective: To investigate the expression of fragilehistidine triad (FHIT) gene and its correlation withclinicopathological features and correlation with mismatchrepair protein (mainly MLH1 and MSH2) in humansporadic colorectal carcinoma (SCC). Methods:Immunohistochemistry SP method was used to determinethe expression of FHIT, MLH1 and MSH2 protein insurgically resected specimens of 84 human SCC. Results:The positive rates of FHIT, MLH1 and MSH2 proteinexpression were 48.81%, 92.86% and 100% respectively.Loss or reduced expression of FHIT protein was not related with tumors clinicopathological features such as age, gender, tumors site and histological type (P>0.05), but wascorrelated with tumors invade depth, degree of thedifferentiation, Ducks?stage and metastasis (P<0.05). There was no relationship between FHIT gene expression andMLH1 protein (r=0.0991, P>0.05) and MSH2 protein(r=0.0000, P=l.00) expression in human SCC. Conclusion:Absent or reduction of FHIT gene expression consists ofhigh proportion and is a frequent event in SCC. FHIT gene is involved in the development and progression of humanSCC and may be a candidate tumors suppressor gene. The relationship between alteration of FHIT gene expression and mismatch repair protein (mainly MLH1 and MSH2)deserved further study in human SCC.