p53蛋白在口腔鳞癌中的表达

目的 通过对突变型p53蛋白在口腔鳞癌组织中表达的观察,分析p53与口腔鳞癌临床病理特征之间的关系,探讨p53在口腔鳞癌发生中的作用机制。方法 利用免疫组化(P-V法)检测116例患者口腔鳞癌组织及10例正常人口腔黏膜组织中突变型p53蛋白的表达情况。结果 p53蛋白在正常人口腔黏膜和口腔鳞癌组织中的表达率分别为20％、63.8％,二者比较差异有统计学意义(X2=5.660 4,P<0.05);口腔鳞癌在不同病理分级时,p53蛋白表达差异有统计学意义(X2=7.536 2,P<0.05);p53蛋白表达与年龄、性别、发生部位及有无淋巴结转移无相关性。结论 突变型p53蛋白表达与口腔鳞癌的发生有关。不同病理分级,p53蛋白表达也不同。     

Expressions of p53, VEGF C,p21: could they be used in preoperative evaluation of lymph node metastasis of esophageal squamous cell carcinoma?

The prognosis of esophageal squamous cell carcinoma is primarily determined by staging. Although radiological methods have revealed lymph node metastasis preoperatively, these radiological findings cannot be correlated with pathological staging. The aim of this study was to compare the expressions of p53, vascular endothelial growth factor C (VEGF C) and p21 with lymph node metastasis in preoperative endoscopic biopsy and postoperative resection material. Tissue samples were taken from 40 patients who had undergone endoscopic biopsies and radical esophagectomies. The expressions of p53, VEGF C and p21 proteins in these sections were immunohistochemically examined. The expression of each antibody was characterized as a negative or positive reaction according to the pattern and intensity of semiquantitative immunostaining. The staining pattern of antibodies was divided into three groups: < 10% cancer cells were accepted to be (-), 10-50% were (+), heterogenous and > 50% were (+ +), homogenous. For each antibody, statistical correlation with conventional prognostic parameters such as localization, microscopic grade, stage, pathological lymph node metastasis and survival, were investigated. p53 expression was observed in 65.5% (19/29) of lymph node positive cases, whereas p53 was in 50% (20/40) of cases. VEGF C was in 65% (26/40) and p21 was in 15% (6/40) of cases. p53 has the specificity of 90.9% and sensitivity rate of 65.5% in detecting lymph node metastasis and positive predictive value was 95%. Expression of p53 was significantly correlated with stage and lymph node metastasis (P = 0.02 and P = 0.03, respectively). Prediction of lymph node metastasis by p53 was correlated independently and in coexpression with VEGF C (P < 0.01). There was no relation detected between p21 and other parameters. In esophageal squamous cell carcinoma (SCC), p53 and VEGF C expressions were correlated with pathologically positive lymph nodes. When preoperative staging has been insufficient in esophageal carcinoma cases, immunohistochemical analysis of p53 and VEGF C staining in tissues could be an aid to clinicians regarding lymph node metastasis.     

A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley

AIM: To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma (ESCC) among the Kashmiri population of Northern India. METHODS: All cases (n=51) and controls (n = 150) were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient's age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls. RESULTS: Thirty-five of 45 (77.8%) histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed germline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 (77.7%), that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance (P<0.05) with familial history of cancer (CD=58), suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable "Hakh" (CD=19.5), red chillies (CD=20.2), hot salty soda tea (CD = 2.37) and local baked bread (CD=1.1). CONCLUSION: Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and "Hakh", that are rich in nitrosoamines and familial cancer history.     

Correlation of plasma miR-21 and miR-93 with radiotherapy and chemotherapy efficacy and prognosis in patients with esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC) is one of the main causes of human death. It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage. Therefore, patients have already lost the best surgical timing when diagnosed. Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically, but the efficacy and prognosis of patients from them are still unsatisfactory. Therefore, it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy, and other 45 healthy people during the same period were enrolled as a control group. The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction,and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed. The receiver operating characteristic(ROC) curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients, the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients, and the Cox regression analysis toidentify the prognostic factors for ESCC patients.RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group(P 0.01). The area under the ROC curve(AUC) of plasma miR-21 for diagnosing T stage, N stage, M stage, and pathological differentiation of ESCC was 0.819, 0.758, 0.824, and 0.725,respectively, and that of plasma miR-93 for diagnosing T stage, N stage, and M stage of ESCC was 0.827, 0.815, and 0.814, respectively. The AUC of combined plasma miR-21 and miR-93 for predicting radiotherapy and chemotherapy efficacy before radiotherapy and chemotherapy was 0.894, and the AUCs of them for predicting the 3-year overall survival(OS) were 0.861 and 0.807, respectively.T stage(P 0.05), M stage(P 0.05), miR-21(P 0.01), and miR-93(P 0.05) were independent risk factors for radiotherapy and chemotherapy efficacy, and T stage(P 0.01), N stage(P 0.05), M stage(P 0.01), miR-21(P 0.01), and miR-93(P 0.01) were independent prognostic factors for ESCC patients.CONCLUSION MiR-21 and miR-93 can be adopted as effective biomarkers for predicting radiotherapy and chemotherapy efficacy in ESCC and the 3-year OS of ESCC patients.     

Changes in p53 and Waf1p21 expression and cell proliferation in esophageal carcinogenesis

AIM: To study the correlation between changes in p53 and Waf1p21 expression and cell proliferation, determined by proliferating cell nuclear antigen (PCNA), at different stages of human esophageal carcinogenesis.METHODS: Biopsied and resected esophageal tissues from a high risk population of esophageal cancer in northern China were used in this study. All specimens were fixed in 85% alcohol and processed for routine histology. The avidin biotin peroxidase complex (ABC) method was used to detect p53, Waf1p21 and PCNA.RESULTS: Strong nuclear staining of p53, Waf1p21 and PCNA was observed in normal esophageal epithelium and epithelia with different lesion severities. As the lesions progressed to dysplasia (DYS) and to esophageal squamous cell carcinoma (SCC), the Waf1p21 immunoreactivity percentage decreased. The number of Waf1p21-positive cells slightly increased from normal to basal cell hyperplasia (BCH), but did not further increase in DYS and SCC. The total number of Waf1p21-positive cells was lower than the number of p53-positive cells in normal and BCH esophageal epithelia and much lower in DYS and SCC. Waf1p21-positive cells were located in the third and fourth cell layers in half of the samples examined, which was 2-4 cell layers higher than the cells expressing PCNA and p53 in the same histological categories of normal, BCH and DYS.CONCLUSION: Low Waf1p21 levels at the DYS stage may be related to a functional loss of p53. Other mechanisms may also be responsible for the decreased Waf1p21 expression in DYS and SCC.     

Expression of thymidylate synthase and glutathione-s- transferase π in patients with esophageal squamous cell carcinoma

AIM： To investigate the expression of thymidylate synthase （TS） and glutathione-s-transferase π （GST-π） in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS： Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma （ESCC） tissue sections from 102 patients （median age, 58 years） and in 28 normal esophageal mucosa （NEM） samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS： The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples （P 〈 0.05）. The expression level of TS was not only significantly lower in well-differentiated （21.88%） than in poorly-differentiated carcinomas （51.43%, P 〈 0.05）, but was also significantly higher in samples from male patients （46.51%） than from female patients （18.75%, P 〈 0.05）. GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples （P 〈 0.05）. The expression level of GST-π was also significantly higher in welldifferentiated carcinomas （65.63%） than in poorly- differentiated carcinomas （35.00%, P 〈 0.05）. CONCLUSION： The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of T5 and reduced expression of GST-π.     

Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemoor radiotherapy prior to surgical resection.Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immuno...     

Association between Bmi1 and clinicopathological status of esophageal squamous cell carcinoma

AIM： To investigate the clinicopathological roles of Bmil in esophageal squamous cell carcinoma （ESCC）.METHODS： Quantitative real-time polymerase chain reaction and immunohistochemical staining for Broil were performed in cancerous and adjacent non-cancerous paraffin-embedded esophageal specimens.RESULTS： The Bmil expression level was unaffected by gender and age. The level of Broil mRNA in ESCC was significantly higher than that in the adjacent non-cancerous tissues （2.181 ± 2.158 vs 0.931 ± 0.894, P = 0.0152）, and its over-expression was aggressively associated with lymph node metastasis （3.580 ± 2.487 vs 1.703 ± 0.758, P = 0.0003）, poorer cell differentiation （P = 0.0000） and advanced pathological stage （3.827± 2.673 vs 1.590 ± 0.735, P = 0.0001）. The patients were divided into high-expression and low-expression groups based on the median expression level of Bmi1 mRNA, and a shorter overall survival time in the former group was observed. Immunohistochemistry for Bmi1 oncoprotein showed diffusely positive, focally positive and negative expression in 44, 16 and 10 of 70 ESCC cases, respectively, compared with three, two and five of 10 adjacent non-cancerous cases （P = 0.027）. The positive rate of the oncoprotein in samples of histological grade Ⅲ was higher than that of grade Ⅱ（P = 0.031）, but its expression had no relation to the lymph node metastasis and pathological staging. In 70 ESCC samples, Bmi1 showed high intense expression in the cytoplasm and less or even no expression in the nucleus.CONCLUSION： Bmi1 was over-expressed in ESCC. Increased Bmi1 mRNA expression was significantly associated with ESCC progression, and the oncoprotein was largely distributed in the cytoplasm of tumor cells.     

Changes of serum p53 antibodies and clinical significance of radiotherapy for esophageal squamous cell carcinoma

AIM： To explore the relationship between serum p53 antibodies （p53-Abs） and clinicopathological characteristics and therapeutic effect in patients with esophageal carcinoma （EC）, and to investigate sequential changing regularity of serum pS3-Abs after radiotherapy.
METHODS： The serum pS3-Ab levels were detected in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay （ELISA）. The blood samples were collected on the day before radiotherapy and on the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and 60 Gy/30 f/36 d after radiotherapy.
RESULTS： The level and positive rate of serum pS3-Abs in EC patients were significantly higher than those in normal individuals （P 〈 0.05）. Serum anti-p53 antibodies were positive in 18 of 46 EC patients （39.1%）. The positive rate of pS3-Abs in EC was related to histological grade, disease stage and lymph node metastasis （P 〈 0.05）, but it was not significantly related to sex, age and to the size and site of tumor. The level and positive rate of p53-Abs had significant differences between before radiotherapy and after administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d （P 〈 0.05 orP 〈 0.01）. The positive rate of p53-Abs in EC patients with effect was significantly lower than that in those without effect after radiotherapy （P 〈 0.0001）.
CONCLUSION： Detection of serum p53-Abs is helpful to the diagnosis of esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before and after radiotherapy in patients with esophageal carcinoma is also useful to evaluate the response to the treatment and prognosis of the patients.     

Clinical significance of matrix metalloproteinase-9 expression in esophageal squamous cell carcinoma

AIM: To evaluate the expression of matrix metalloproteinase-9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by immunohistochemistry (IHC) and its clinical significance in ESCC especially the relationship with the clinicopathological parameters was analyzed. RESULTS: The percentage of positive cases for MMP-9 detected by IHC was 49.0%. MMP-9 was mainly expressed in the cytoplasm of cancer cells especially in the invasive front. Only weak expression was detected in the stromal cells and no expression in non-cancerous mucosa. The expression of MMP-9 was positively correlated with poorer differentiation (P= 0.001<0.01), existence of vessel permeation (P= 0.027<0.05) and lymph node metastasis (P=0.027<0.05). CONCLUSION: The expression of MMP-9 correlates with the cancer cell differentiation, vessel permeation and lymph node metastasis. It may be a novel biomarker for the diagnosis and treatment of ESCC.     

Specific intronic p53 mutation in esophageal squamous cell carcinoma in Southern Thailand

AIM:To investigate p53 mutations in esophageal cancer in a high-risk population,and correlate them with smoking,alcohol consumption and betel chewing.METHODS:One hundred and sixty-five tumor samples of esophageal squamous cell carcinoma(ESCC) obtained from a university hospital in Songkhla province,Southern Thailand were investigated for p53 mutations in exons 5-8,using polymerase chain reaction-single strand conformation polymorphism analysis,followed by direct sequencing.A polymerase chain reactionrestric...     

Smo和Gli1蛋白在食管鳞状细胞癌组织中的表达及临床意义

目的:探讨Sonic hedgehogq信号通路中Smo和Glil蛋白在食管鳞状细胞癌(ESCC)组织中的表达及临床意义.方法:采用免疫组织化学二步法分别检测60例ESCC、45例癌旁异型增生及60例食管正常黏膜组织中Smo和Glil蛋白的表达,并分析两者的表达水平与临床病理因素的关系.结果:Smo和Glil蛋白在ES...     

P53 gene codon 72 polymorphism and risk of esophageal squamous cell carcinoma: a case/control study in a Chinese population

SUMMARY.  The aims of this study were to investigate whether p53 gene codon 72 polymorphism was a biomarker associated with esophageal squamous cell carcinoma (ESCC) and its relationship with smoking status in China. The p53 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism among 673 patients with ESCC and 694 healthy controls. The association between p53 genotypes and risk of developing ESCC was estimated by odds ratios (OR) and their 95% confidence intervals (CIs) computed by logistic regression. Compared with Arg/Arg homozygotes, Pro/Pro homozygotes had a nearly twofold increased risk (adjusted OR, 1.83; 95% CI, 1.35–2.48). For the Pro/Arg heterozygotes, there was no evident increased risk (adjusted OR, 1.01, 95% CI, 0.78–1.30). Furthermore, the risk associated with the Pro/Pro variant genotype was more pronounced in younger patients at diagnosis (= 45 years) (OR, 7.4; 95% CI, 1.44–37.89, P  = 0.02), in women (OR, 3.15; 95% CI, 1.52–4.53, P  = 0.02) and in non-smokers (OR, 2.49; 95% CI, 1.58–3.94) and light smokers (OR, 2.13; 95% CI, 1.15–3.93). But tests for homogeneity between smoking-related OR showed no significant differences ( P  = 0.4). The p53 gene codon 72 Pro/Pro genotype was significantly associated with the increased risk of ESCC in a Chinese mainland population and may be an independent factor in susceptibility to ESCC. The association was especially noteworthy in women and in younger patients.     

曲古抑菌素A对甲状腺鳞癌SW579细胞株p53和p21表达的影响

目的观察曲古抑菌素A(TSA)对甲状腺鳞癌SW579细胞株生长增殖及p53和p21表达的影响,进而探讨TSA抗甲状腺癌的作用机制。方法体外培养SW579细胞,实验分为DMSO组、TSA组(终浓度为50、100、200、400 nmol/L),采用MTT比色法测定细胞增殖活性;用RT-PCR方法检测SW579细胞p53及p21的mRNA表达;用Western blot方法检测SW579细胞p53及p21的蛋白表达。结果 MTT结果显示,TSA可明显抑制SW579的增殖,并呈剂量依赖性。RT-PCR与Western blot检测结果表明,与未加TSA组比较,TSA组随着浓度的逐渐加大,p21 mRNA和蛋白表达水平明显升高;p53 mRNA表达不变,而p53蛋白表达水平上调。结论 TSA在一定浓度范围内对甲状腺鳞癌细胞株SW579有剂量依赖性地增殖抑制作用,其机制可能与TSA提高SW579细胞p53的表达,进而再上调p21的表达有关。     

Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

AIM: To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis.METHODS: Using real-time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features.RESULTS: Immunohistochemically, OCT4 positive immunostaining was observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27 (17.6%) were strongly positive. Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001).CONCLUSION: The expression of OCT4 enables the tumor to have a higher degree of stemness, which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.     

SOX2在食管鳞癌组织中的表达及意义

目的:探讨食管鳞癌组织中SOX2 mRNA和蛋白的表达及意义.方法:应用原位杂交和免疫组织化学法分别检测35例正常食管黏膜组织及84例食管鳞癌组织中SOX2 mRNA和蛋白的表达.结果:SOX2在正常黏膜组织中mRNA的表达率为8.6％(3/35),显著低于其在癌组织中的表达率46.4％(39/84),组间比较差异具有...     

p53 negativity, CDC25B positivity, and metallothionein negativity are predictors of a response of esophageal squamous cell carcinoma to chemoradiotherapy

AIM: Esophageal squamous cell carcinoma is generally sensitive to chemoradiotherapy (CRT), but some cases are not. Using a retrospective analysis, we aimed to identify the predictors of the response by esophageal squamous cell carcinoma to definitive CRT. METHODS: The intensities of expression of,p53, Ki67, Bcl-2, Bax, cyclin D1, VEGF, CDC25B, and metalbthionein (MT) were evaluated immunohistochemically in the bfopsy specimens obtained before CRT, and the intensities of their expression were tested for correlations with the clinical effects of CRT. RESULTS: The esophageal squamous cell carcinomas with negative p53, positive CDC25B, and negative MT expression were found to be significantly more sensitive to CRT. In addition, p53 positivity and CDC25B positivity respomd well to CRT. CONCLUSION: Esophageal squamous cell carcinomas with negative p53,positive CDC25B, and negative MT expressions respond well to CRT. Even with p53 positivity, if with CDC25B positivity, CRT can be expected.     

Overexpression of Ets-like protein 1 in human esophageal squamous cell carcinoma

INTRODUCTION Esophageal cancer ranks among the 10 most frequent cancers in the world, with a predominant distribution in developing countries. It is one of the most common malignant tumors in China[1,2]. Our previous study showed that genetic susceptibili…