Primary adenosquamous carcinoma of the esophagus

AIM:To investigate the clinical characteristics,diagnosis,treatment,and prognosis of primary adenosquamous carcinoma(ASC)of the esophagus.METHODS:A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College.In 37 cases,the histological diagnosis was primary ASC.Clinical data were retrospectively analyzed from these 37 patients,who underwent transthoracic esophagectomy with lymphadenectomy.Theχ2or Fisher’s exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma(SCC).The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates.A Cox proportional hazard regression model was used to identify independent prognostic factors.RESULTS:Primary esophageal ASC accounted for0.92%of all primary esophageal carcinoma cases(37/4015).The clinical manifestations were identical to those of other types of esophageal cancer.All of the 24patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC.The median survival time(MST)was 21.0 mo(95%CI:12.6-29.4),and the1-,3-,and 5-year overall survival rates were 67.5%,29.4%,and 22.9%,respectively.In multivariate analysis,only adjuvant radiotherapy(HR=0.317,95%CI:0.114-0.885,P=0.028)was found to be an independent prognostic factor.The MST for ASC patients was significantly lower than that for SCC patients[21.0 mo(95%CI:12.6-29.4)vs 46.0 mo(95%CI:40.8-51.2),P=0.001].In subgroup analyses,the MST for ASC patients was similar to that for poorly differentiated SCC patients.CONCLUSION:Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy.The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.     

Esophageal squamous cell carcinoma and aldehyde dehydrogenase-2 genotypes in Japanese females

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) is the key enzyme for elimination of acetaldehyde, an established animal carcinogen produced after drinking. In persons with inactive ALDH2, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Inactive heterozygous ALDH2 enhances the risk of esophageal squamous cell carcinoma (SCC) in Japanese male drinkers. METHODS: We studied whether this is the case for women. The risk factors of esophageal SCC were examined in 52 Japanese women with esophageal SCC and 412 cancer-free Japanese women. RESULTS: The increasing trend in cancer risk according to the quantity of alcohol consumption was significantly steeper in women with inactive heterozygous ALDH2 than in those with active ALDH2 [adjusted odds ratios (ORs) (95% confidence intervals (CIs)) per +7 U/wk increment of alcohol drinking were 3.91 (2.09-7.31) and 1.39 (0.92-2.09), respectively; p = 0.006 for difference in OR; 1 Ut = 22 g of ethanol]. The results obtained using an alcohol-flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping [adjusted ORs (95% CIs) per +7 U/wk increment of alcohol drinking were 3.94 (1.87-8.31) and 1.46 (0.96-2.23) in those with and without flushing, respectively; p = 0.021 for difference in OR]. The risk of esophageal cancer was markedly higher in heavy drinkers with ALDH2*1/*2 than in never/rare drinkers with ALDH2*1/*1 [adjusted OR (95% CI) = 59.1 (4.65-750)]. Other independent significant risk factors of esophageal SCC were smoking, a preference for hot food or drinks, and lower intake of green and yellow vegetables. CONCLUSIONS: Japanese men and women shared several common risk factors of esophageal SCC, including drinking with inactive heterozygous ALDH2.     

Detection of anti-CUEC-23 antibodies in serum of patients with esophageal squamous cell carcinoma: a possible new serum marker for esophageal cancer

Background  Serological identification of antigens by recombinant cDNA expression cloning (SEREX) is an established method for detecting new tumor-specific antigens. Antibodies to SEREX antigens may be useful for the detection of esophageal squamous cell carcinoma (SCC). Methods  A phage cDNA library of a human esophageal SCC cell line was screened using sera of patients with esophageal SCC. The presence and levels of serum antibodies to SEREX antigens were established by Western blotting and enzyme-linked immunosorbent assay (ELISA) using purified recombinant antigen proteins, respectively. Results  The newly identified esophageal SCC antigen is encoded by a novel gene located on chromosome 1, here designated CUEC-23. Serum CUEC-23-antibodies (s-CUEC-23-Abs) were detected in 14 of 54 patients with esophageal SCC (26%) by Western blot analysis. Esophageal SCCs were positive for s-CUEC-23-Abs together with CEA, SCC-Ag or CYFRA21-1 in 44, 41 and 52% of cases, respectively. There was no detectable association between the presence of s-CUEC-23-Abs and clinicopathological variables. ELISA showed that the levels of s-CUEC-23-Abs were significantly higher in patients with esophageal SCC than in healthy volunteers (17% in the former using the mean + 3 SD of s-CUEC-23-Abs in healthy controls as the cutoff). Conclusion  A new tumor antigen, CUEC-23, was identified by SEREX screening. s-CUEC-23-Abs might be a useful serum marker to detect esophageal SCC. This study identified a new tumor antigen, CUEC-23, detected on esophageal squamous cell carcinoma cells. CUEC-23 antibody was found in the serum of patients with esophageal squamous cell carcinoma and might be a useful tumor marker to detect this cancer.     

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.     

Epstein-Barr virus association is rare in esophageal squamous cell carcinoma

Background. A critical role of Epstein-Barr virus (EBV) in carcinogenesis of nasopharyngeal squamous cell carcinoma and gastric adenocarcinoma is strongly suspected. We analyzed the possible EBV association for Japanese squamous cell carcinoma (SCC)-dominant esophageal cancer cases. Methods. We retrospectively screened 36 surgically resected esophageal cancer lesions from 36 patients maily with SCC using in situ hybridization (ISH) for EBV-encoded small RNA1 (EBER-1). EBV DNA analysis using real-time quantitative polymerase chain reaction (Q-PCR) was performed for three recent cases. Results. We found no EBER-1-positive cancer cell in any tested esophageal cancer lesion. There were many EBER-1-positive tumor-infiltrating lymphocytes in the basaloid SCC lesion and a small number of positive lymphocytes in the other five advanced SCC lesions (14.7% of SCC). One SCC lesion with a highcopy number of EBV DNA had EBER-1-positive lymphocytes. Conclusions. EBV is rarely associated with esophageal SCC, and may appear through tumor-infiltrating lymphocytes in some advanced lesions.     

Unchanging pattern of prevalence of esophageal cancer,overall and by histological subtype,in the endoscopy service of the main referral hospital in the central region of Rio Grande do Sul State,in Southern Brazil

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the two main histological types of esophageal cancer. Southern Brazil has the highest rates of esophageal cancer in South America, and the most prevalent subtype of esophageal cancer has been SCC. This study assessed the trend changes in the histological types of esophageal cancer, in a 20‐year period, in the central region of Rio Grande do Sul State, Brazil. We searched all cases of esophageal cancer from 1993 to 2012 by their histological diagnosis, grouping the patients in 4‐year time periods to evaluate time trends. Among 18 441 upper gastrointestinal endoscopies we identified 686 cases of esophageal cancer. Histological study confirmed the diagnosis of SCC in 640 (93.3%) patients and ADC in 46 (6.7%). Overall, 522 men were diagnosed with esophageal carcinoma; from these, 489 (93.6%) presented SCC, and 33 (6.3%) ADC. Among women, 164 had the diagnosis of esophageal cancer, 151 (92%) SCC, and 13 (7.9%) ADC. The proportion found among men and women was 3.1:1, respectively. The prevalence rate of esophageal cancer, along a 20 year‐period, remained stable, as well as the rates of SCC and ADC. SCC was the most common type of esophageal cancer, and ADC presented very low prevalence.     

Implantation of esophageal cancer onto post-dissection ulcer after gastric endoscopic submucosal dissection

A case in which implantation of esophageal squamous cell carcinoma onto a post-dissection gastric ulcer was strongly suspected is presented. A 72-yearold man with alcoholic liver cirrhosis underwent esophagogastroduodenoscopy(EGD). Esophageal cancer(EC)(Mt, 20 mm, 0-Is) and gastric cancer(GC)(antrum, 15 mm, 0-Ⅱc) were identified. Biopsy specimens revealed moderately differentiated squamous cell carcinoma(SCC) and differentiated adenocarcinoma, respectively. The GC was resected by endoscopic submucosal dissection(ESD) [14 mm × 9 mm, type 0-Ⅱc, tub1, p T1a(M), ly0, v0, HM(-), VM(-)]. Two months after ESD, radiation therapy was started for the EC, and an almost complete response was obtained. Nine months after the ESD, a follow-up EGD showed a submucosal tumor-like lesion with ulceration, located immediately under the post-ESD scar, and biopsy specimens showed moderately differentiated SCC. There were no similar lesions suggesting hematogenous or lymphatic metastasis in the stomach.     

Esophageal melanosis, an endoscopic finding associated with squamous cell neoplasms of the upper aerodigestive tract, and inactive aldehyde dehydrogenase-2 in alcoholic Japanese men

Background Esophageal melanosis is often observed in alcoholic Japanese men, in whom the prevalence of squamous cell dysplasia and carcinoma (SCC) in the upper aerodigestive tract are high. This study evaluated the associations of esophageal melanosis with these neoplasms, and the factors contributing to the development of esophageal melanosis in this population.Methods Endoscopic screening was combined with esophageal iodine staining in 1535 alcoholic Japanese men (aged 40–79 years), of whom 1007 underwent aldehyde dehydrogenase-2 (ALDH2) genotyping.Results Fifty patients (3.3%) were diagnosed with esophageal melanosis, which had a higher incidence in those with noncancerous distinct iodine-unstained lesions (DIULs; 16/268; 6.0%), esophageal SCC (9/66; 13.6%), and oropharyngolaryngeal SCC (4/19; 21.1%) than in cancer- and DIUL-free controls (24/1182; 2.0%). The presence of esophageal melanosis was associated with higher risks for noncancerous DIULs, esophageal SCC, and oropharyngolaryngeal SCC (odds ratios, 2.81, 6.54, and 14.77, respectively). Men with the inactive ALDH2*1/2*2 genotype had a higher risk for esophageal melanosis (2.66-fold), as well as for DIULs and SCCs.Conclusions The presence of esophageal melanosis in alcoholic Japanese men could indicate a high risk for DIULs and SCCs in the upper aerodigestive tract. The high incidence of esophageal melanosis may be partially linked to high acetaldehyde exposure, a consequence of drinking alcohol in persons with inactive ALDH2.     

Expressions of PCNA, p53, p21WAF-1and cell proliferation in fetal esophageal epithelia： Comparative study with adult esophageal lesions from subjects at high-incidence area for esophageal cancer in Henan, North China

AIM: To characterize the expression of p53, p21WAF-1 and proliferation-cell-nuclear-antigen (PCNA) in fetal esophageal epithelia and to determine the role of these genes in proliferation of fetal and adult esophageal epithelial cells. METHODS: Immunohistochemical avdin-biotin peroxidase complex (ABC) method was applied to 31 cases of fetal esophageal specimens and 194 cases of adult esophageal specimens to detect the expression of p53, p21WAF-1 and PCNA in fetal and adult esophageal epithelia. RESISTS: Both the PCNA positive immunostaining cell number and PCNA positive immunostaining rate in fetal esophageal epithelia (5064-239) were significantly higher than those in adults, induding normal epithelia (2004-113) and epithelia with basal cell hyperplasia (BCH) (2864-150) (P<0.05, ttest). However, the number of PCNA positive immunostaining cells in adult esophageal dysplasia (7194-389) and squamous cell cardnoma (SCC) (12614-545) was apparently higher than that in fetal esophageal epithelia (5064-239) (P<0.05, tbest). The positive immunostaining rabe of P53 was 10 % (3/31) in fetal esophageal epithelia, which was significantly lower than that in adult normal esophageal epithelia (50 %), adult epithelia with basal cell hyperplasia (62 %), dysplasia (73 %) and squamous cell carcinoma (86 %) (P<0.05, Fisher‘‘s exact test). No p21WAF-l positive immunostaining cells were observed in fetal esophageal epithelia. However, p21w~l positive immunost~ining cells wereobserved in adult esophagus with 39 % (11/28) in normal, 38% (14/37) in BCH, 27 % (3/11) in DYS and 14 % (1/7) in SCC. CONCLUSION: PCNA could act as an indicator accurately reflecting the high proliferation status of fetal esophageal epithelium, p53 may play an important role in growth and differentiation of fetal esophageal epithelium, p21WAF-1 may have no physiological function in development of fetal esophageal epithelium.     

Immunohistochemical expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in squamous cell carcinoma of the esophagus.

BACKGROUND/AIMS: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor which is an angiogenic factor. We attempted to clarify the significance of dThdPase expression in esophageal squamous cell carcinoma (SCC). METHODOLOGY: Tissues samples were taken from 50 patients with esophageal SCC after curative surgery. The expression of dThdPase was immunohistochemically examined using a monoclonal antibody to dThdPase (clone 654-1). Microvessels in SCC stained for Factor VIII-related antigen were counted. Vascular endothelial growth factor (VEGF) was immunostained with R11. Ki-67 antigen was immunostained with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed, and Ki-67 labeling index (LI) and apoptotic index were calculated. RESULTS: The expression of dThdPase was observed in 30 patients (60%). Between the SCC with and without dThdPase expression, significant differences were found in microvessel count (p < 0.001) and VEGF expression (p < 0.01), but not in Ki-67 LI and apoptotic index. With regard to the clinicopathologic factors, significant differences were observed in histologic venous invasion (p < 0.01) and lymph node metastasis (p < 0.05). Survival rate after surgery was better in the patients with dThdPase-negative SCC (p < 0.05), and distant organ metastasis after surgery was frequently observed in the patients with dThdPase-positive SCC (p < 0.05). CONCLUSIONS: These results suggest that dThdPase expression may be associated with angiogenic promotion and may be one of the prognostic factors in esophageal SCC.     

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC pa     

Clinical usefulness of CYFRA 21-1 for esophageal squamous cell carcinoma in radiation therapy

AIM: The aim of this study was to examine the clinical usefulness of cytokeratin 19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in patients with esophageal cancer treated with radiation therapy. METHODS: Fifty-one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC antigen serum levels were measured at the start and the end of radiation therapy. RESULTS: CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21-1 levels were significantly correlated with TNM stages, tumor depth and lymph node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no correlation was observed between SCC antigen and these factors. The values of CYFRA 21-1 in all patients who survived without recurrence were under the cutoff level at the end of treatment, but the values in all patients with locoregional recurrence were above the level. However, there was no significant correlation between SCC antigen level at the end of treatment and any clinical outcome. CONCLUSIONS: The results suggest that the evaluation of CYFRA 21-1 would be useful not only for assessment before radiation therapy but also for monitoring after radiation therapy in the treatment for esophageal cancer.     

Association between Helicobacter pylori seropositivity and digestive tract cancers

AIM: To explore the role of Helicobacter pylori ( H pylori) infection on the risk of digestive tract cancers.METHODS: In total, 199 oral squamous-cell carcinoma (SCC), 317 esophageal SCC, 196 gastric cardia and non-cardia adenocarcinoma and 240 colon adenocarcinoma patients were recruited for serum tests of H pylori infection.Two hospital- and one community-based control groups were used for the comparisons.H pylori seropositivity was determined by an enzyme linked immunosorbent assay method against H pylori IgG.RESULTS: Presence of H pylori infection was signifi- cantly inversely associated with esophageal SCC [adjusted odds ratio (AOR): 0.315-0.472, all P-value < 0.05] but positively associated with gastric adenocarcinoma (both cardia and non-cardia) (AOR: 1.636-3.060, all P-value < 0.05) in comparison to the three control groups.Similar results were not found in cancers of the oral cavity and colon.CONCLUSION: Our findings support the finding that H pylori seropositivity is inversely associated with esophageal SCC risk, but increases the risk of gastric cardia adenocarcinoma.     

Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma

AIM: To investigate the role of cytochrome P450 (CYP) in the carcinogenesis of squamous-cell carcinoma (SCC) in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. METHODS: mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC (n = 21) and in controls (n = 10). Protein levels of CYP2E1, CYP2C8, CYP3A4, and CYP3A5 were measured by Western blot. RESULTS: Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue (-39% and -74%, respectively, P < 0.05) than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients (4.8-, 2.9-, and 1.9-fold elevation, P < 0.05) than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients (+46%, P < 0.05). CONCLUSION: Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue (e.g. CYP2C8, CYP3A4, CYP3A5, and CYP2E1) between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.     

Have patients with esophagitis got an increased risk of adenocarcinoma？ Results from a population-based study

AIM: To examine an increased risk of esophageal adenocarcinoma is restricted to patients who develop Barrett's esophagus or whether esophagitis per is a risk factor for adenocarcinoma. METHODS: A population-based cohort of patients with histological evidence of esophagitis without Barrett's esophagus was constructed using electronic pathology reports relating to all esophageal biopsies in Northern Ireland between 1993 and 1996. Person-years of follow-up and incident cases of esophageal cancer were calculated by linking the cohort to death files and the Northern Ireland Cancer Registry records. Standardized incidence ratios (SIR) were calculated for esophageal cancers (adenocarcinoma, squamous cell carcinoma (SCC), and historically unspecified cancers). RESULTS: A total of 2 013 patients in the cohort provided 13 559 patient-years of follow-up (mean follow-up 6.7 years). None of the patients developed adenocarcinoma. Three patients developed SCC, and six developed histologically unspecified cancers. The SIR for all esophageal cancers and for SCC were 2.73 (95%CI 1.25-5.19) and 2.93 (95%CI 0.61-8.59), respectively. In a sensitivity analysis in which all unspecified esophageal cancers were treated as adenocarcinomas, the SIR for adenocarcinoma was 2.64 (0.97-5.75). CONCLUSION: The risk of adenocarcinoma is not elevated in patients with histological evidence of esophagitis without Barrett's esophagus; however, these patients may have a moderately increased risk of SCC. Further studies are required to confirm these findings, which suggest that Barrett's esophagus, not esophagitis, is the key precursor lesion in the development of adenocarcinoma.     

Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin

AIM: To determine the effects of curcumin, (-)-epigallocatechin-3-gallate (EGCG), lovastatin, and their combinations on inhibition of esophageal cancer.METHODS: Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin, EGCG and lovastatin treatment. Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines, tumor xenografts and human esophageal cancer tissues, respectively.RESULTS: These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro. Molecularly, these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2), c-Jun and cyclooxygenase-2 (COX-2), but activated caspase 3 in esophageal cancer cells. The nude mouse xenograft assay showed that EGCG and the combinations of curcumin, EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67, phosphorylated Erk1/2 and COX-2. The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry. The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein. In particular, phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma, while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION: The combinations of curcumin, EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts, these drugs also inhibited phosphorylated Erk1/2, c-Jun and COX-2 expression.     

Histochemical study of angiogenesis in basaloid squamous carcinoma of the esophagus

Angiogenesis of esophageal basaloid squamous carcinoma (BSC) was studied immunohistochemically and compared with that of squamous cell carcinoma (SCC). In tissues taken from six patients with esophageal BSC and 35 with esophageal SCC, angiogenesis was evaluated by measuring microvessel density (MVD), defined as the microvessel count determined using factor VIII-related antigen immunostaining, and by measuring immunoreactivity of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase). Three of the six patients with BSC had distant metastases. There was no difference of MVD between BSC and SCC (22.0 +/- 4.6 vs. 27.6 +/- 9.4). VEGF expression tended to be more frequently observed in BSC than in SCC (100% vs. 60.0%; p = 0.066). Strong expression of VEGF was detected in three BSC with distant metastases; however, there was no difference in the rate of strong VEGF expression between BSC and SCC. The MVD in the cases of BSC with strong VEGF expression, i.e. in the cases with distant metastases, was higher than that in the cases of BSC with weak VEGF expression (p=0.049). There was no difference in dThdPase expression of the cancer cells between BSC and SCC (50.0% vs. 54.3%), whereas the infiltrating stromal cells of all the BSC expressed dThdPase. Strong dThdPase expression in the cancer cells or in the infiltrating stromal cells was observed in two and three BSC, respectively. However, there were no differences in the rate of cancer cells or stromal cells with strong dThdPase expression between BSC and SCC. In one BSC with high MVD and distant metastases, VEGF and dThdPase were both strongly expressed. The vascularity of esophageal BSC was not different from that of SCC. VEGF may participate in angiogenesis of esophageal BSC and may influence the rate of metastasis in esophageal BSC patients. dThdPase may play a partial rule in angiogenesis and metastasis in some cases of BSC.     

Prognostic factors in patients with recurrence after complete resection of esophageal squamous cell carcinoma

Background

Recurrence following complete resection of esophageal squamous cell carcinoma (SCC) still remains common. The aim of this study was to investigate the prognostic factors in patients with recurrence after complete resection of esophageal SCC.

Methods

The medical records of 190 patients with recurrent disease after complete resection of esophageal SCC were retrospectively reviewed. Recurrence pattern was classified as loco-regional recurrence and distant metastases. The Kaplan-Meier method was used for the survival analysis. Cox proportional hazards model was used for multivariate analysis.

Results

Mediastinal nodal clearance area was the most common sites of loco-regional recurrence, whereas lung, liver and bone were the most common sites for distant metastases. The median survival after recurrence was 8 months. The 1, 3, 5-year post-recurrence survival rates were 45.9%, 10.6% and 6.4%, respectively. The overall 1, 3, 5-year survival rates were 76.6%, 27.3% and 12.3%, respectively. The independent prognostic factors included time of recurrence (≥12 months vs. <12 months, HR: 3.228, 95% CI: 2.233-4.668), pattern of recurrence (local-regional recurrence vs. distant metastases, HR: 1.690, 95% CI: 1.170-2.439), and treatment of recurrence [no treatment vs. treatment (radiotherapy or surgery or chemotherapy), HR: 0.642, 95% CI: 0.458-0.899].

Conclusions

Our retrospective study showed that time of recurrence, pattern of recurrence and treatment of recurrence were independent prognostic factors in patients with recurrence after complete resection of esophageal SCC.     

Induction of prostaglandin E synthase by gastroesophageal reflux contents in normal esophageal epithelial cells and esophageal cancer cells

The synthesis of prostaglandin E2 (PGE2) requires cyclooxygenase (COX) and prostaglandin E synthase (PGES). There are two forms of PGES: cytosolic PGES (cPGES) and microsomal PGES (mPGES)-1. In this study, we investigated the effects of gastroesophageal reflux (GER) contents on PGES and COX-2 in esophageal cells. We incubated a human normal esophageal cell line, two esophageal squamous cell carcinoma (SCC) cell lines, and two esophageal adenocarcinoma (ADC) cell lines with GER contents. The production of PGE2 by these cells was assayed with an enzyme immunoassay kit. The protein expression of COX-2, cPGES, and mPGES-1 was confirmed by immunoblot analysis. The following results were obtained: GER contents induced the expression of COX-2 in all five cell lines. In normal esophageal cells, cPGES, but not mPGES-1, was detected in the cytosolic fraction. GER contents induced the expression of cPGES in the microsomal fraction. In SCC cells, cPGES was expressed in the cytosolic fraction, and mPGES-1 was expressed in the microsomal fraction. GER contents induced the expression of mPGES-1 in the microsomal fraction. In ADC cells, cPGES was expressed in both the cytosolic and microsomal fractions. GER contents induced the expression of both cPGES and mPGES-1 in the microsomal fraction. In conclusion, our results suggest that GER contents induce PGE2 production in esophageal cells. However, there are different isoforms of PGES in normal cells, SCC cells, and ADC cells.     

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.