Diagnosis Of Esophageal Squamous Cell Carcinoma Research Articles

Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma

BackgroundEarly diagnosis of esophageal squamous cell carcinoma (ESCC) is an important issue to improve the prognosis. HOX transcript antisense RNA (HOTAIR), a long noncoding RNA (lncRNA) expressed from the HOXC locus, has been recently revealed as an oncogenic regulator in ESCC. This study aimed to investigate whether serum HOTAIR is involved in the diagnosis of ESCC.MethodsIn this study, we detected serum HOTAIR expression in 50 patients with ESCC (including 42 tumor resection and 8 without surgery) and 20 healthy volunteers to investigate the role of serum HOTAIR in ESCC using the quantitative real-time polymerase chain reaction (qRT-PCR) method.ResultsClinical data indicated that serum HOTAIR were correlated with TNM stage. The expression level of serum HOTAIR (0.189 ± 0.010) was significantly higher in ESCC patients compared with that of healthy controls (0.055 ± 0.008, P < 0.01). The ROC curve analysis yielded an area under the ROC curve (AUC) value of 0.793 (95% CI: 0.692 to 0.895, P < 0.01). Also, the serum HOTAIR expression level decreased obviously in postoperative samples (one month after the surgery) compared to preoperative specimens. Moreover, there was a significant correlation between serum HOTAIR expression and the expression of HOTAIR in ESCC tissue according to Pearson correlation analysis.ConclusionsOur study, for the first time, demonstrated that serum HOTAIR might serve as a potential biomarker for the diagnosis of ESCC.

Candidate susceptibility variants for esophageal squamous cell carcinoma.

Esophageal cancer is common worldwide, and often fatal. The major histological subtype is esophageal squamous cell carcinoma (ESCC). ESCC shows familial aggregation and high heritability. Mutations in RHBDF2 cause tylosis, a very rare disorder characterized by high life-time risk of ESCC, but no other well-established predisposition genes have been identified. To identify candidate susceptibility variants for ESCC we utilized the Population Information System and the Finnish cancer registry to find study materials by clustering ESCC patients by family name at birth and municipality at birth. We collected archival tissue material and exome sequenced a total of 30 ESCC cases. We prioritized shared, deleterious and rare variants that were significantly enriched in our sample set compared to Finnish and population subset specific controls. Six variants passed filtering, the most frequent being a nonsense mutation in DNAH9 (p.Tyr1573Ter) found in four unrelated patients. DNAH9 has been reported to be frequently lost in ESCC tumors. In this study, one patient's tumor showed loss of the wild type allele of DNAH9 suggesting a tumor suppressive function. A missense variant in GKAP1 was shared by three patients, and missense variants in BAG1, NFX1, FUK, and DDOST by two each. EP300 which has previously been implicated in the genesis of ESCC had a missense variant segregating in three affected individuals in a single family. If validated in independent patient sets, these variants could serve as a tool towards prevention and early diagnosis of ESCC.

A six-microRNA signature in plasma was identified as a potential biomarker in diagnosis of esophageal squamous cell carcinoma.

The differential expression of microRNAs (miRNAs) in plasma of esophageal squamous cell carcinoma (ESCC) patients may serve as a diagnostic biomarker. A four-stage study was conducted to identify plasma miRNAs with potential in detecting ESCC. Exiqon panels (2 ESCC pools vs. 1 normal control (NC) pool) were applied in the screening phase to obtain miRNA profiles. The identified miRNAs were further evaluated through training (36 ESCC VS. 42 NCs) and testing stages (101 ESCC VS. 113 NCs) with qRT-PCR assays. A six-miRNA signature including up-regulated miR-106a, miR-18a, miR-20b, miR-486-5p, miR-584 and down-regulated miR-223-3p in ESCC was identified. The signature could accurately discriminate ESCC patients from NCs with areas under the receiver operating characteristic curve of 0.935, 0.959 and 0.966 for the training, testing and the additional validation stage (41 ESCC VS. 50 NCs), respectively. MiR-106a and miR-584 were significantly up-regulated in tumor tissues with qRT-PCR assays. And miR-584 was also up-regulated in ESCC tissues from TCGA database. In addition, exosomal miR-223-3p and miR-584 were consistently dysregulated with those in plasma and could also act as biomarkers in diagnosis of ESCC. In conclusion, we identified a six-miRNA signature in plasma which could act as a non-invasive biomarker in detection of ESCC.

Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and clinical outcomes. We previously showed that conditioned medium (CM) from CAFs induces proliferation and motility of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the molecular mechanisms by which the CAF-secreted proteins induce ESCC development and progression. Using antibody arrays, we identified urokinase plasminogen activator (uPA) as one of the main proteins whose release was increased in CAFs compared to normal fibroblasts (NFs). Immunohistochemical analysis of pathological sections showed that uPA-positive cells were localized at the boundaries of tumor and stroma tissues, in stroma between tumor nests, and within the tumors. Increased stromal uPA levels (132/146 cases) correlated with tumor invasion (p < 0.05) and overall survival of ESCC patients (p < 0.05). In vitro assays showed that uPA promotes ESCC cell proliferation, migration, and invasion via PI3K/AKT and ERK signaling pathways. In vivo, anti-uPA antibody suppressed tumor growth in ESCC xenografts. These results suggest that uPA released from stroma, and especially from CAFs, might be a predictive marker for ESCC diagnosis and prognosis, as well as an effective therapeutic target.

Correlation between secreted protein acidic and rich in cysteine protein expression and the prognosis of postoperative patients exhibiting esophageal squamous cell carcinoma.

The aim of the present study was to investigate the association between the expression level of secreted protein acidic and rich in cysteine (SPARC) and the prognosis of postoperative patients with esophageal squamous cell carcinoma (ESCC). The expression level of SPARC was detected in the 89 ESCC tissue cases and 100 healthy esophageal mucosa cases, which served as the controls. Immunohistochemistry and reverse transcription‑polymerase chain reaction (RT‑PCR) were employed to evaluate the SPARC expression in cases with ESCC. RT‑PCR demonstrated that the positive rates of SPARC mRNA expression in ESCC were 71.91% (64/89). The positive rates of normal esophageal mucosa mRNA expression were 15.00% (15/100), which were significantly lower than that in the ESCC tissue samples. The difference was statistically significant (P<0.001). Immunohistochemical staining indicated that the positive expression rate of SPARC protein in the ESCC tissue samples was significantly higher than that in the esophageal mucosa tissue samples (65.17 vs. 8.00%; P<0.001). The expression of SPARC protein was negatively correlated with lymph node metastasis (P<0.05), which was not associated with the pathologic gross morphology, tumor differentiation degree or other clinical features. The survival of patients with ESCC was not associated with the expression level of SPARC protein (P>0.05), but was associated with the tumor location (P<0.05), differentiation (P<0.001) and staging (P<0.05). Thus, SPARC mRNA and protein were highly expressed in ESCC, and negatively correlated with lymph node metastasis, which was not associated with postoperative survival of ESCC patients. Thus, detection of SPARC mRNA and protein expression levels may facilitate early diagnosis and prognosis assessment of ESCC.

Circulating levels of autoantibodies against L1-cell adhesion molecule as a potential diagnostic biomarker in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a common malignant disease worldwide, especially in China. We aimed to determine the level of autoantibodies against L1CAM in patients with ESCC. Levels of circulating autoantibodies against L1CAM antigens were determined by an enzyme-linked immunosorbent assay in cohort 1 (191 patients with ESCC and 94 normal controls) and validated in cohort 2 (47 patients with ESCC and 47 normal controls). Receiver-operating characteristics were employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. In cohorts 1 and 2, levels of autoantibodies against L1CAM were all significantly higher in sera of patients with ESCC compared to normal controls (P<0.05). Detection of autoantibodies against L1CAM provided a sensitivity of 26.2%, a specificity of 90.4%, and an area under the curve (AUC) of 0.603 (95% CI 0.535-0.672) in diagnosing ESCC in cohort 1, and a sensitivity of 27.7%, a specificity of 91.5%, and an AUC of 0.628 (95% CI 0.516-0.741). Similar results were observed in the diagnosis of early stage ESCC (25.2% sensitivity, 90.4% specificity, and an AUC of 0.611 (95% CI 0.533-0.689) in cohort 1, and 33.3% sensitivity, 91.5% specificity, and an AUC of 0.636 (95% CI 0.439-0.832) in cohort 2). Moreover, positive rates of autoantibodies against L1CAM had no statistical correlation with clinical outcome of ESCC (P>0.05). Our results suggest that circulating autoantibodies against L1CAM is a potential biomarker for the early detection of ESCC.

MicroRNA-196a as a Potential Diagnostic Biomarker for Esophageal Squamous Cell Carcinoma

ABSTRACTWe observed significant up-regulation of miR-196a in esophageal squamous cell carcinoma (ESCC) as compared with their adjacent normal tissue (p = .002). Receiver operating characteristics curve analysis confirmed the suitability of miR-196a as a potential tumor marker for diagnosis of ESCC. Furthermore, analysis of miR-196a levels in saliva samples determined an average of 27-fold up-regulations in ESCC patients compared with healthy group. Our results suggest that salivary miR-196a may be a suitable noninvasive biomarker for diagnosis of ESCC. In addition, molecular pathway enrichment analysis of microRNA (miR)-196a determined focal adhesion, spliceosome and p53 signaling pathways as the most relevant pathways with miR-196a targetome.

Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P < 0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P < 0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.

Truth telling for patients with esophageal squamous cell carcinoma in Henan, China.

Objective: This study aims to investigate the truth-telling status and the relevant factors of esophageal squamous cell carcinoma (ESCC) patients in Henan, China.Methods: A cross-sectional study from April to June 2015 using questionnaires was given to 301 family members of hospitalized ESCC patients based in three affiliated hospitals of Zhengzhou University (i.e., The First Hospital, The Second Hospital, and Tumor Hospital) and Anyang Tumor Hospital.Results: Among the 41.9% (126/301) hospitalized ESCC patients who knew of their true diagnoses, only 4.0% patients were informed by their corresponding responsible doctors, 39.7% by their family members, and 56.3% by themselves. Univariate analyses showed that disclosure of confirmed ESCC diagnosis to patients was correlated with gender, family history of cancer (FHC), education level, vocation, hospital administrative level, and attitudes of family members (P < 0.05). Furthermore, multivariate analysis indicated that attitude of family members was the most important and an independent factor for diagnosis disclosure. Those patients with a negative FHC, under-education, manual occupation, advanced stages, and hospitalized in municipal hospitals exhibited a low rate of truth telling. Conclusions: Truth telling for ESCC patients in Henan is not prevalent and may be improved through consultation with family members, particularly for patients with a negative FHC, poor education, manual occupation, and advanced stages.

Development and Validation of a Serum Biomarker Panel for the Detection of Esophageal Squamous Cell Carcinoma through RNA Transcriptome Sequencing.

Serum tumor markers for the diagnosis of esophageal squamous cell carcinoma (ESCC) have low sensitivity. This study aims to identify new serum markers for ESCC diagnosis from RNA sequencing (RNA-seq) data.RNA-seq was performed using six pairs of ESCC and matched normal tissues. The candidates for ESCC were screened from the differentially expressed genes. The candidates were analyzed by ELISA from the serum of a test group and a validation group. Real-time PCR, Western blotting and immunohistochemistry were used to detect the expression of the candidates in tumor cell lines and tumor tissues.Ten genes were selected from the RNA-seq data. Serum levels of ADAM12, CHI3L1, MMP13 and SPP1 were significantly higher in the ESCC patients than in the healthy controls. A diagnostic model combining CHI3L1, MMP13, and SPP1 was established. The area under the curve (AUC) values for serum CHI3L1, MMP13, and SPP1 and the diagnostic model for discriminating ESCC patients from controls were 0.732, 0.881, 0.661 and 0.928, respectively. In the validation cohort, the AUC values were 0.753, 0.789, 0.696 and 0.843, respectively. Moreover, the AUC of the model for classifying patients with early ESCC was 0.918 in the test group and 0.857 in the validation group. Overexpression of CHI3L1, MMP13 and SPP1 was observed in the tumor cell lines and tissues.The diagnostic model composed of CHI3L1, MMP13 and SPP1 discriminates ESCC patients with high sensitivity. Our data highlight the potential of this diagnostic model for the noninvasive diagnosis of ESCC.

H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma.

Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. In our study, we found that lncRNA CCAT1, whose expression is significantly increased and is correlated with outcomes in Esophageal Squamous Cell Carcinoma (ESCC). Consecutive experiments confirmed that H3K27-acetylation could activate expression of colon cancer associated transcript-1 (CCAT1). Further experiments revealed that CCAT1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. RNA-seq analysis revealed that CCAT1 knockdown preferentially affected genes that are linked to cell proliferation, cell migration and cell adhesion. Mechanistic investigations found that CCAT1 could serve as a scaffold for two distinct epigenetic modification complexes (5΄ domain of CCAT1 binding Polycomb Repressive Complex 2 (PRC2) while 3΄ domain of CCAT1 binding SUV39H1) and modulate the histone methylation of promoter of SPRY4 (sprouty RTK signaling antagonist 4) in nucleus. In cytoplasm, CCAT1 regulates HOXB13 as a molecular decoy for miR-7, a microRNA that targets both CCAT1 and HOXB13, thus facilitating cell growth and migration. Together, our data demonstrated the important roles of CCAT1 in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy.

Expressions of Mel-18 and Bmi-1 in esophageal squamous cell carcinoma and their clinical significance

Objective To analyze the expression levels and clinicopathological significances of Mel-18 and Bmi-1 in esophageal squamous cell carcinoma (ESCC) tissues and paired normal mucosal tissues. Methods The expression levels of Mel-18 and Bmi-1 were measured by real-time PCR and Western blot in ESCC tissues and pericarcinous tissues from 29 patients with ESCC. ESCC tissues and pericarcionous tissues from 60 ESCC patients in chip library were collected too. The expressions of Mel-18 and Bmi-1 protein in 89 ESCC specimens were analyzed by immunohistochemistry. The relationship between Mel-18 and Bmi-1 expressions and the clinicopathological parameters of ESCC were analyzed. Results The real-time PCR showed that the negative expression rate of Mel-18 mRNA was 55.17% (16/29) and the positive expression rate of Bmi-1 mRNA was 62.07% (18/29) in ESCC tissue. Western blot indicated that the level of Mel-18 protein was significantly lower (0.724±0.095 vs. 0.899±0.089, t=2.319, P=0.028), while the level of Bmi-1 was significantly higher (0.980±0.068 vs. 0.729±0.066, t=2.863, P=0.008) in ESCC tissues than that in pericarcinous tissues. The immunohistochemistry showed that the negative expression rate of Mel-18 protein [66.3% (59/89) vs. 31.5% (28/89), χ2=21.606, P<0.05] and the positive expression rate of Bmi-1 [74.2% (66/89) vs. 30.3% (27/89), χ2=34.249, P<0.05] in ESCC tissues were significantly higher than those in pericarcinous tissues. The Mel-18 expression was correlated with clinical stage (χ2=8.003, P=0.004), depth of invasion (χ2=17.094, P=0.001) and lymph node metastasis (χ2=5.156, P=0.026). The Bmi-1 expression has a correlation with the differentiation degree (χ2=14.625, P=0.001), clinical stage (χ2=7.863, P=0.005) and lymph node metastasis (χ2=5.771, P=0.005). In addition, there were negative correlations between Mel-18 and Bmi-1 in ESCC according to results of real-time PCR and immunohistochemistry (r=-0.592, P=0.001; r=-0.285, P=0.007). Conclusions The expression level of Mel-18 was significantly lower, and the expression level of Bmi-1 was significantly higher in ESCC tissues compared with those in para-carcinoma tissues. Mel-18 and Bmi-1 may be the new biomarkers for diagnosis and prognosis of ESCC. Key words: Esophageal neoplasms; Carcinoma, squamous cell; Mel-18; Bmi-1

Accumulated promoter methylation as a potential biomarker for esophageal cancer.

We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965–1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928–1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC.

A newly developed continuous zoom-focus endocytoscope.

Background and study aims We report the features of a newly developed endocytoscopy system (ECS), the GIF-Y0074. Patients and methods The GIF-Y0074 offers high-definition resolution with a consecutive increase of magnification to × 500. Using ECS, we observed 32 cases of esophageal squamous cell carcinoma (ESCC), 11 cases of gastric cancer, and five cases of duodenal adenoma. Results The images of cells obtained using the GIF-Y0074 at maximum magnification were brighter and clearer than those obtained with previous ECS systems. For diagnosis of ESCC, clearer visualization of the nucleus made nuclear abnormality easier to recognize. Cancer cells were visualized in 10/11 cases of gastric cancer, but removal of mucus still remained a problem. Duodenal adenomas were found to have atypical cells with villi and tubules at the mucosal surface, thus assisting their histological diagnosis in vivo. Conclusion The GIF-Y0074 is an excellent ECS in terms of ease of use, satisfactory resolution, and magnification power, and therefore achieves a level of utility that makes its commercial release justifiable. This ECS heralds a new era of endoscopic and histological diagnosis.

Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging.

We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

Diagnostic accuracy of probe-based confocal laser endomicroscopy in Lugol-unstained esophageal superficial lesions of patients with head and neck cancer

Surveillance programs of patients with head and neck cancer (HNC) detect synchronous or metachronous esophageal squamous cell carcinoma (ESCC) in up to 15% of patients. Noninvasive, probe-based confocal laser endomicroscopy (pCLE) technique may improve the diagnosis allowing acquisition of high-resolution invivo images at the cellular and microvascular levels. The aim of this study was to evaluate the accuracy of pCLE for the differential diagnosis of nonneoplastic and neoplastic Lugol-unstained esophageal lesions in patients with HNC. Twenty-seven patients with HNC who exhibited Lugol-unstained esophageal lesions at surveillance endoscopy were prospectively included for pCLE. Diagnostic pCLE was followed by subsequent biopsies or endoscopic resection of suspected lesions. A senior pathologist was blinded to the pCLE results. Patients mean age was 59 years (SD= 8.8) and 70.4% were men. All patients were smokers, and 22 patients (81.5%) had a history of alcohol consumption. The locations of HNC were oral cavity (n= 13), larynx (n= 10), and pharynx (n= 4). Thirty-seven lesions in 27 patients were studied. The final diagnoses were ESCC in 17 patients and benign lesions in 20 patients. Sensitivity, specificity, and accuracy of pCLE for the histologic diagnosis of ESCC in patients with HNC were 94.1%, 90.0%, and 91.9%, respectively. First, pCLE is highly accurate for real-time histology of Lugol-unstained esophageal lesions in patients with HNC. Second, pCLE may alter the management of patients under surveillance for ESCC, guiding biopsies and endoscopic resection, avoiding further diagnostic workup or therapy of benign lesions.

HER-2/neu Overxpression in Esophageal Squamous Cell Carcinoma (ESCC) and Its Correlation with Patient’s Clinicopathological Features

Background: HER-2/neu overexpression has been reported in various human cancers and identified as a significant predictor of poor survival. In this study HER-2/neu overexpression and its associations with clinicopathological characteristics were evaluated in patients with esophageal squamous cell carcinoma (ESCC). Methods: This cross-sectional study was performed on 64 patients with histological diagnosis of primary ESCC who underwent surgery for curative treatment. Immunohistochemistry (IHC) was used to assess expression of HER-2/neu receptor in formalin-fixed paraffin-embedded tissue blocks. Results: The mean age of patients was 60.1 ± 1.28 years. The overall HER2 expression was observed in 51.5% of ESCC patients without considering IHC scores. HER2/neu overexpression (6%) was significantly associated with the tumor differentiation (P < 0.001). 20.3% of cases were stage I, 67.2% stage II, and 12.5% stage III. 17 patients (26.2%) had vascular invasion, 12 patients (18.8%) had neuronal invasion and 7 patients (10.9%) had invasion to margins. Nine of 12 patients with HER-2/neu over expression had thoracic tumors and only three of them had an abdominal ESCC. Conclusions: No significant correlations were found between HER2/neu overexpression and gender, age, tumor invasion, location of tumor, TNM stages and stage of tumor in patients with ESCC.

Expressions and clinicopathological significances of BMI-1 and PADI4 in esophageal squamous cell carcinoma

Objective To evaluate the expression levels of peptidylarginine deiminase 4 (PADI4) and B-cells pecific Moloney leukemia virus insert site-1 (BMI-1) in esophageal squamous cell carcinoma (ESCC) tissues and pericarcinous tissues. To explore the function and clinical significance in the development of ESCC and their association. Methods The expression levels of PADI4 and BMI-1 were measured by immunohistochemistry, Western blotting and quantitative real time PCR in ESCC tissues and pericarcinous tissues from 86 patients. The relationships between the expressions of PADI4 and BMI-1 and the clinicopathologic characte-ristics were analyzed. Results The immunohistochemistry showed that the expressions of PADI4 and BMI-1 in ESCC tissues (68.6% and 73.3%) were significantly higher than those in pericarcinous tissues (37.2% and 30.2%, χ2=17.011, P=0.000; χ2=31.876, P=0.000). Western blotting indicated that the levels of PADI4 and BMI-1 were higher than those in pericarcinous tissues (0.919±0.098 vs. 0.718±0.103, t=2.462, P=0.021; 0.975±0.074 vs. 0.717±0.071, t=2.640, P=0.014). The expressions of BMI-1 and PADI4 mRNA in ESCC tissues were higher than those in pericarcinous tissues, but the differences were not statistically significant (0.091±0.005 vs. 0.038±0.002, t=1.701, P=0.101; 0.114±0.075 vs. 0.048±0.003, t=1.499, P=0.146) by the quantitative real time PCR. The expression of PADI4 was correlated with lymph node metastasis (χ2=5.771, P=0.016), depth of invasion (χ2=6.672, P=0.010) and clinical stage (χ2=5.771, P=0.016). The BMI-1 gene expression had a correlation with lymph node metastasis (χ2=7.176, P=0.007), the differentiation degree (χ2=13.787, P=0.001) and clinical stage (χ2=7.176, P=0.007). In addition, there was a positive correlation between PADI4 and BMI-1 expression in ESCC by immunohistochemistry and quantitative real time PCR (r=0.214, P=0.047; r=0.534, P=0.005). Conclusion The expression levels of PADI4 and BMI-1 are significantly higher in ESCC compared to pericarcinous tissues. PADI4 and BMI-1 are positively correlated and may contribute to the diagnosis and prognosis of the ESCC. Key words: Esophageal neoplasms; Peptidylarginine deiminase 4; B-cells pecific Moloney leukemia virus insert site-1

Population attributable fraction of Esophageal squamous cell carcinoma due to smoking and alcohol in Uganda.

BackgroundDespite the high rates and regional variation of esophageal squamous cell carcinoma (ESCC) in East Africa, the contributions of smoking and alcohol to the ESCC burden in the general population are unknown.MethodsWe conducted a case-control study of patients presenting for upper gastrointestinal endoscopic examination at Mbarara Regional Referral Hospital, Uganda. Sociodemographic data including smoking and alcohol intake were collected prior to endoscopy. Cases were those with histological diagnosis of ESCC and controls were participants with normal endoscopic examination and gastritis/duodentitis or normal histology. We used odds ratios associated with ESCC risk to determine the population attributable fractions for smoking, alcohol use, and a combination of smoking and alcohol use among adults aged 30 years or greater who underwent upper gastrointestinal endoscopy.ResultsOur study consisted of 67 cases and 142 controls. Median age was 51 years (IQR 40–64); and participants were predominantly male (59 %). Dysphagia and/or odynophagia as indications for endoscopy were significantly more in cases compared to controls (72 % vs 6 %, p < 0.0001). Male gender and increasing age were statistically associated with ESCC. In the unadjusted models, the population attributable fraction of ESCC due to male gender was 55 %, female gender - 49 %, smoking 20 %, alcohol 9 % and a combination of alcohol & smoking 15 %. After adjusting for gender and age, the population attributable fraction of ESCC due to smoking, alcohol intake and a combination of alcohol & smoking were 16, 10, and 13 % respectively.ConclusionIn this population, 13 % of esophageal squamous cell carcinoma cases would be avoided if smoking and alcohol use were discontinued. These results suggest that other important risk factors for ESCC in southwestern Uganda remain unknown.