Importance of early detection of esophageal cancer before the tumor progresses too much for effective treatment

This editorial comments on an article by Qu et al published in the World Journal of Gastrointestinal Oncology.It focuses on the importance of early detection of esophageal cancer,including recurrence or secondary malignancy after chemoradiotherapy(CRT).Endoscopic resection is the first choice for treatment for esophageal cancer remaining within the mucous membrane,while surgery or radical CRT are treatment options for advanced stages depending on the patient’s general condition and desire.Although these treatments are potentially curative,they are more invasive than endoscopic resection.Early-stage esophageal cancer is often asymptomatic and difficult to detect.Uniform periodic endoscopy is unrealistic.Although less burdensome tests exist,including liquid biopsy and urinary biomarkers,these have not yet been widely used in clinical practice.Early detection is important after radical CRT because the local recurrence rate is higher than that after surgery.However,endoscopic resection or photodynamic therapy is indicated if detected in the early stages,and positive results have been reported.Early detection of esophageal cancer is crucial.Endoscopy is the main diagnostic method;however,new and less burdensome methods should be established to ensure early treatment for patients with esophageal cancer.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Combination of concurrent endoscopic submucosal dissection and modified peroral endoscopic myotomy for an achalasia patient with synchronous early esophageal neoplasms

with an increased risk for developing esophageal squamous cell carcinoma. In our paper, we introduced an achalasia patient combined with synchronous early esophageal neoplasms. We performed a combination of concurrent endoscopic submucosal dissection (ESD) and peroral endoscopic myotomy (POEM). No complications other than postoperative pain that needed morphine treatment for two days had occurred. Dysphagia was significantly improved. Neither reflux nor cough occurred. The short-term efficacy and safety of our case is favorable and suggests that concurrent ESD and POEM could be a treatment option to such patients.

Diagnostic value of conventional endoscopic ultrasound for lymph node metastasis in upper gastrointestinal neoplasia:A metaanalysis

BACKGROUND Upper gastrointestinal neoplasia mainly includes esophageal cancer and gastric cancer,both of which have high morbidity and mortality.Lymph node metastasis(LNM),as the most common metastasis mode of both diseases,is an important factor affecting tumor stage,treatment strategy and clinical prognosis.As a new fusion technology,endoscopic ultrasound(EUS)is becoming increasingly used in the diagnosis and treatment of digestive system diseases,but its use in detecting LNM in clinical practice remains limited.AIM To evaluate the diagnostic value of conventional EUS for LNM in upper gastrointestinal neoplasia.METHODS Using the search mode of“MeSH+Entry Terms”and according to the predetermined inclusion and exclusion criteria,we conducted a comprehensive search and screening of the PubMed,EMBASE and Cochrane Library databases from January 1,2000 to October 1,2022.Study data were extracted according to the predetermined data extraction form.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool,and the results of the quality assessment were presented using Review Manager 5.3.5 software.Finally,Stata14.0 software was used for a series of statistical analyses.RESULTS A total of 22 studies were included in our study,including 2986 patients.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic score and diagnostic odds ratio of conventional EUS in the diagnosis of upper gastrointestinal neoplasia LNM were 0.62[95%confidence interval(CI):0.50-0.73],0.80(95%CI:0.73-0.86),3.15(95%CI:2.46-4.03),0.47(95%CI:0.36-0.61),1.90(95%CI:1.51-2.29)and 6.67(95%CI:4.52-9.84),respectively.The area under the summary receiver operating characteristic curve was 0.80(95%CI:0.76-0.83).Sensitivity analysis indicated that the results of the meta-analysis were stable.There was considerable heterogeneity among the included studies,and the threshold effect was an important source of heterogeneity.Univariable meta-regression and subgroup analysis showed that tumor type,sample size and EUS diagnostic criteria were significant sources of heterogeneity in specificity(P<0.05).No significant publication bias was found.CONCLUSION Conventional EUS has certain clinical value and can assist in the detection of LNM in upper gastrointestinal neoplasia,but it cannot be used as a confirmatory or exclusionary test.

Correlation between c-erbB-2 and P-glycoprotein Expression in Esophageal Carcinoma

Objective： To investigate the correlation between c-erbB-2 and multidrug resistance （MDR） and its clinical significance, Methods： Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow cytometry was used to detect the expression of P-glycoprotein （P-gp） in samples from 46 patients with esophageal carcinoma. Results： The positive expression rate of c-erbB-2 was 26.1% （12/46） in the 46 cases of esophageal carcinoma, of which 4 cases being low expression and 8 cases mediumhigh expression. The positive expression rate of P-gp was 60.9% （28/46） in the 46 cases of esophageal carcinoma, of which 6 cases being low expression, 13 cases medium expression and 9 cases high expression. Comparing c-erbB-2 with P-gp expression in different lymph node metastasis statuses showed that there was significant difference （P〈0.01） between P-gp expressions with lymph node metastasis （31.09%±5.33%） and without lymph node metastasis （8.04%±3.03%） when c-erbB-2 expression was positive. Comparing c-erbB-2 with P-gp expression in different TNM stages of esophageal carcinoma showed that there was significant difference （P〈0.01） between P-gp expressions in HI Ⅳ stage （33.68%±5.51%）and in Ⅱ stage patients （9.30%±2.78%） when c-erbB-2 expression was positive. The tumor＇s size and differentiation degree were not related to c-erbB-2 and P-gp expression. Conclusion： The high level of P-gp expression was related to the positive expression of c-erbB-2 with the lymph node metastasis in clinical Ⅲ-Ⅳ stage patients of esophageal carcinoma, suggesting that the double positive might lead to a poor prognosis. However, when the c-erbB-2 expression was negative, the lymph node metastasis and clinical staging were not related to the P-gp expression in esophageal carcinoma patients.

Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma

AIM:To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis.METHODS:PubMed and manual searches were done to identify all published randomized controlled trials(RCTs) that compared neoadjuvant chemoradiotherapy plus surgery(CRTS) with surgery alone(S) for esophageal cancer.According to the test of heterogeneity,a fi xed-effect model or a random effect model was used and the odds ratio(OR) was the principal measure of effects.RESULTS:Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C(Cochrane Reviewers' Handbook 4.2.2).OR(95% CI,P value),expressed as CRTS vs S(values>1 favor CRTS arm),was 1.19(0.94-1.48,P=0.28) for 1-year survival,1.33(1.07-1.65,P=0.69) for 2-year survival,1.76(1.42-2.19,P=0.11) for 3-year survival,1.41(1.06-1.87,P=0.11) for 4-year survival,1.64(1.28-2.12,P=0.40) for 5-year survival,0.82(0.39-1.73,P<0.0001) for rate of resection,1.53(1.33-2.84,P=0.007) for rate of complete resection,1.78(1.14-2.78,P=0.79) for operative mortality,1.12(0.89-2.48,P=0.503) for all treatment mortality,1.33(0.94-1.88,P=0.04) for the rate of adverse treatment,1.38(1.23-1.63,P=0.0002) for local-regional cancer recurrence,1.28(0.85-1.58,P=0.60) for distant cancer recurrence,and 1.27(0.86-1.65,P=0.19) for all cancer recurrence.A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients.The 5-year survival benefi t was most pronounced when chemotherapy and radiotherapy were given concurrently(OR:1.45,95% CI:1.26-1.79,P=0.015) instead of sequentially(OR:0.85,95% CI:0.64-1.35,P=0.26).CONCLUSION:Compared with surgery alone,neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence.Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.

Relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaoshan inhabitants of China

AIM:To study the relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaoshan inhabitants of China, which is a unique Littoral high-risk area of esophageal carcinoma in China. The poor communication and transportation in the past has made Chaoshan a relatively closed area and kept its culture and custure of old China thousand years ago. METHODS: Data on age, sex, ABO blood type and X-ray or pathological diagnose of the patients with carcinoma of esophagus or cardia were collected from the Tumor Hospital. First Affiliated Hospital, Second Affiliated Hospital of Shantou University Medical College; and the Central Hospital of Shantou and the Central Hospital of Jieyang. A total of 6685 patients with esophageal carcinoma (EC) and 2955 patients with cardiac cancer (CC) in Chaoshan district were retrospectively assessed for their association with ABO blood groups. RESULTS: The distribution of ABO blood groups in patients with EC or CC was similar to the normal local population in Chaoshan. However, blood group B in male patients with CC and in the patients with carcinoma in the upper third esophagus was 2.3% and 4.7% higher than the corresponding controls. The relative risk B O was 1.1415 (P【0.05) and 1.2696 (P【0.05), respectively. No relationship was found between ABO blood groups and tumor differentiation. CONCLUSION: ABO blood group B is associated with the incidence of CC in male individuals and carcinoma in the upper third esophagus. The distribution of ABO blood groups varies in the different geographical and ethnic groups. As a result, proper controls are very important for such studies.

Transcription factor EGR-1 inhibits growth of hepatocellular carcinoma and esophageal carcinoma cell lines

AIM: The transcription factor EGR-1 (early growth response gene-1) plays an important role in cell growth, differentiation and development. It has identified that EGR-1 has significant transformation suppression activity in some neoplasms, such as fibrosarcoma, breast carcinoma. This experiment was designed to investigate the role of egr-1 in the cancerous process of hepatocellular carcinoma (HCC) and esophageal carcinoma (EC), and then to appraise the effects of EGR-1 on the growth of these tumor cells. METHODS: Firstly, the transcription and expression of egr-1 in HCC and EC, paracancerous tissues and their normal counterpart parts were detected by in situ hybridization and immunohistochemistry, with normal human breast and mouse brain tissues as positive controls. Egr-1 gene was then transfected into HCC (HHCC, SMMC7721) and EC (ECa109) cell lines in which no egr-1 transcription and expression were present. The cell growth speed, FCM cell cycle, plate clone formation and tumorigenicity in nude mice were observed and the controls were the cell lines transfected with vector only. RESULTS: Little or no egr-1 transcription and expression were detected in HCC, EC and normal liver tissues. The expression of egr-1 were found higher in hepatocellular paracancerous tissue (transcription level P=0.000; expression level P=0.143, probably because fewer in number of cases) and dysplastic tissue of esophageal cancer (transcription level P=0.000; expression level P=0.001). The growth rate of egr-1-transfected HHCC (HCC cell line) cells and ECa109 (EC cell line) cells was much slower than that of the controls. The proportion of S phase cell, clone formation and tumorigenicity were significantly lower than these of the controls' (decreased 45.5% in HHCC cells and 34.1% in ECa109 cells; 46.6% and 41.8%; 80.4% and 72.6% respectively). There were no obvious differences between SMMC7721 (HCC) egr-1-transfected cells and the controls with regard to the above items. CONCLUSION: The decreased expression of egr-1 might play a role in the dysregulation of normal growth in the cancerous process of HCC and EC. Egr-1 gene of transfected HHCC and ECa109 cells showed obvious suppression of the cell growth and malignant phenotypes, but no suppression in SMMC7721 (HCC cell line) cells.

Expression of G3BP and RhoC in esophageal squamous carcinoma and their effect on prognosis

AIM: To investigate the expression and significance of G3BP and RhoC proteins in esophageal squamous carcinoma (ESC). METHODS: The expression of G3BP and Rhoc proteins in 80 cases of ESC was detected by immunohistochemistry. The relationship was studied between the expression of the two proteins and tumor size, differentiation degree, TNM stage, lymph node metastasis and prognosis of ESC. RESULTS: The positive expression rate of G3BP in ESC was 71.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non- lymph node metastasis group (Z = -2.283, P = 0.022), but no relations were found between G3BP expression and tumor size, differentiation degree and TNM stage (P > 0.05). The group with G3BP positive expression had shorter survival time than the group with G3BP negative expression (P = 0.000). The positive expression rate of RhoC in ESC was 66.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (Z = -2.115, P < 0.05), but no relations were found between RhoC expression and tumor size, differentiation degree and TNM stage (P > 0.05). The RhoC positive expression group had a shorter survival time than the RhoC negative expression group (P < 0.001. The expression of G3BP protein correlated positively with the expression of RhoC in ESC tissues (rs = 0.656, P < 0.001). CONCLUSION: The expression of G3BP and RhoC protein is closely related to the lymph node metastasis and survival in ESC patients. G3BP and RhoC proteins can be considered as predictors of prognosis in ESC patients.

Narrow-band imaging without magnification for detecting early esophageal squamous cell carcinoma

AIM：To compare narrow-band imaging（NBI）without image magnification,and chromoendoscopy with Lugol＇s solution for detecting high-grade dysplasia and intramu-cosal esophageal squamous cell carcinoma（SCC）in patients with head and neck cancer.METHODS：This was a prospective observational study of 129 patients with primary head and neck tumors consecutively referred to the Gastrointestinal Endoscopy Unit of Hospital das Clínicas,Sao Paulo University Medical School,Brazil,between August 2006 and Feb-ruary 2007.Conventional examinations with NBI and Lugol chromoendoscopy were consecutively performed,and the discovered lesions were mapped,recorded and sent for biopsy.The results of the three methods were compared regarding sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood value and negative likelihood value.RESULTS：Of the 129 patients,nine（7%）were diag-nosed with SCC,5 of which were in situ and 4 which were intramucosal.All carcinomas were detected through NBI and Lugol chromoendoscopy.Only 4 le-sions were diagnosed through conventional examination,all of which were larger than 10 mm.CONCLUSION：NBI technology with optical filters has high sensitivity and high negative predictive value for detecting superficial esophageal SCC,and produces results comparable to those obtained with 2.5%Lugol chromoendoscopy.

Annual cost of illness of stomach and esophageal cancer patientsin urban and rural areas in China： A multi-center study

Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness （ACI）was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars（1 USD：6.6423 RMB）.Results： Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions： The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.

Minimally invasive surgery for upper gastrointestinal cancer: Our experience and review of the literature

Minimally invasive surgery (MIS) for upper gastrointestinal (GI) cancer, characterized by minimal access, has been increasingly performed worldwide. It not only results in better cosmetic outcomes, but also reduces intraoperative blood loss and postoperative pain, leading to faster recovery; however, endoscopically enhanced anatomy and improved hemostasis via positive intracorporeal pressure generated by CO2 insufflation have not contributed to reduction in early postoperative complications or improvement in long-term outcomes. Since 1995, we have been actively using MIS for operable patients with resectable upper GI cancer and have developed stable and robust methodology in conducting totally laparoscopic gastrectomy for advanced gastric cancer and prone thoracoscopic esophagectomy for esophageal cancer using novel technology including da Vinci Surgical System (DVSS). We have recently demonstrated that use of DVSS might reduce postoperative local complications including pancreatic fistula after gastrectomy and recurrent laryngeal nerve palsy after esophagectomy. In this article, we present the current status and future perspectives on MIS for gastric and esophageal cancer based on our experience and a review of the literature.

Experimental and clinic-opathologic study on the relationship between transcription factor Egr-1 and esophageal carcinoma

AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore the potential application of Egr-1 gene in gene therapy of tumor. METHODS: Eukaryotic expression vector of PCMV-Egr-1 plasmid was introduced into Eca109 cell line which expressed no Egr-1 protein originally with lipofectamine transfection method. The introduction and expression of PCMV-Egr-1 plasmid into Eca109 cell line was confirmed by G418 selection culture, PCR amplification of neogene contained in the vector, Western blot analysis and immunocytochemical analysis. The cell growth curve, soft agar colony formation rate and tumorigenicity in SCID mice were examined to demonstrate the growth suppression effect of exogenous Egr-1 gene on Eca109 cell line. The Egr-1 mRNA and Egr-1 protein were also detected in 50 surgical specimens of esophageal carcinoma by in situ hybridization and immunohistochemistry. RESULTS: Exogenous Egr-1 gene was introduced successfully into Eca109 cell line and expressed Egr-1 protein stably. The transfected Eca109 cell line grew more slowly than control Eca109 as shown by cell growth curves, the soft agar colony formation rate (4.0% vs 6.9%, P 【 0.01) and the average growth rate of tumor in SCID mice (35.5 +/- 7.6 vs 65.8 +/- 7.6, P 【 0.05). The expression level of Egr-1 mRNA and protein significantly increased in dysplastic epithelia adjacent to cancer rather than in cancer tissues (65.8% vs 20.0% by ISH and 57.9% vs 0.01). CONCLUSION: Exogenous Egr-1 gene shows the strong effect of growth inhibition in Eca109 cell line. Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma.

Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma

AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cyclin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors. METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immun-ohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (×200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections. RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immuno-staining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t = 13.32 and t = 7.52, respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t = 3.5675 and t = 3.916; t = 2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping. CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.

Oesophageal surgery

INTRODUCTIONThe origins of oesophageal surgery ,like most surgical treatments ,are based in the treatment of traumatic injury .The Smith Surgical Papyrus describes the examination, diagnosis and treatment of 'a gaping wound of throat, penetrating the gullet' [1].

Identification of human papillomavirus in esophageal squamous papillomas

AIM： To investigate the presence of human papillomavirus （HPV） in esophageal squamous papilloma （ESP） and determine p16, p53 and Ki67 expression in a Mexican cohort. METHODS： Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by ,amplified chromogenic in situ hybridization （ACISH） using a wide spectrum-cocktail probe and PCR. RESULTS： The average age at presentation was 46.3 years （range 28-72 years）. Patients included four （22.22%） males and 14 （77.77%） females. The most frequent location was upper third （11 cases）, followed by middle third （3 cases） and unknown site （5 cases）. Immunohistochemistry （IHC） revealed basal and focal p53 expression in 17 cases （89%）; p16 was expressed in eight cases （42.10%） and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases （87.5%） by ACISH： Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases （85.7%）. Low-risk HPV types were detected in the most of the cases. CONCLUSION： This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESR .

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma(ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450 K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1,CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.

Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63is amplified in early carcinogenesis but down-regulated as disease progressed

AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear. METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status. RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (±0.69); CCNL1: 5.24 (±0.67); SMC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12); hTERC. 5.28 (±0.54); SKIL 2.71 (±0.14); EIF5A2. 1.95 (±0.12); ECT2: 9.18 (±1.68); PIK3CA: 8.13 (±1.17); EIF4G1: 1.07 (±0.05); 557: 3.07 (±0.25); TP63: 2.51 (±0.22); TFRC. 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and 55T, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis. CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.