Search

Background and Study Aim: This study aimed to evaluate endoscopic findings using non-magnifying blue laser imaging (BLI) to determine the risk factors for metachronous esophageal squamous cell carcinoma (ESCC)., Patients and Methods: All consecutive patients who underwent endoscopic submucosal dissection (ESD) for primary superficial ESCC (SESCC) without a history of ESCC between January 2013 and January 2016 were enrolled. Three highly experienced endoscopists investigated seven endoscopic findings using non-magnifying BLI as follows: (1) a brownish area with unclear margin, (2) white flat deposits, (3) multiple foci of dilated vessels, (4) low capillary permeability, (5) multiple glycogenic acanthosis, (6) horizontal lines, and (7) a nonuniform color tone. Furthermore, Lugol-voiding lesions (LVLs) were graded according to the number of LVLs per endoscopic view (A, no lesions; B, 1-9 lesions; C, ≥ 10 lesions)., Results: A total of 102 SESCC patients who underwent ESD were included. Multivariate analyses showed that multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone were significantly associated with metachronous ESCC (hazard ratio [HR] 2.30; 95% confidence interval [CI] 1.01-5.46; P = 0.049, HR 5.25; 95% CI 1.86-15.01; P = 0.002 and HR 3.17; 95% CI 1.11-9.43; P = 0.032, respectively). The three-year cumulative incidence of metachronous ESCC was significantly higher in patients with low capillary permeability and a nonuniform color tone than in patients without these findings. (41.1% vs. 6.0%, 45.0% vs. 12.7%, respectively, P < 0.001 for both)., Conclusion: BLI findings of multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone in the background esophageal mucosa were risk factors for patients with metachronous ESCC after ESD., (© 2021. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride (Cl - ) anion conducting channel, and its role in esophageal squamous cell carcinoma (ESCC) was examined in the present study., Methods: Overexpression experiments were conducted on human ESCC cell lines following the transfection of a CFTR plasmid, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. A microarray analysis was performed to examine gene expression profiles. Fifty-three primary tumor samples collected from ESCC patients during esophagectomy were subjected to an immunohistochemical analysis., Results: Transfection of the CFTR plasmid into the ESCC KYSE 170 and KYSE 70 cell lines suppressed cell proliferation, migration, and invasion and induced apoptosis. The microarray analysis showed the up-regulated expression of genes involved in the p38 signaling pathway in CFTR plasmid-transfected KYSE 170 cells. Immunohistochemical staining revealed a relationship between the CFTR expression pattern at the invasive front and the pN category. A relationship was also observed between the weak expression of CFTR at the invasive front and a shorter postoperative survival in a prognostic analysis., Conclusions: The overexpression of CFTR in ESCC activated the p38 signaling pathway and was associated with a good patient prognosis. These results indicate the potential of CFTR as a mediator of and/or a biomarker for ESCC., (© 2021. Society of Surgical Oncology.)

Background: Chloride channel 2 (CLCN2) was recently shown to affect tumor behavior. The present study examined the functions of CLCN2 in the regulation of genes that play a role in tumor progression, as well as its clinicopathological significance in esophageal squamous cell carcinoma (ESCC)., Methods: Knockdown experiments were conducted using CLCN2-small-interfering RNA, and changes in proliferation, survival, and cellular movement in human ESCC cell lines were investigated. A microarray analysis of gene expression profiles in CLCN2-depleted ESCC cells was conducted. Fifty-four primary ESCC samples were examined by immunohistochemistry (IHC)., Results: The strong expression of CLCN2 was detected in TE5 and KYSE70 cells. Downregulated expression of CLCN2 enhanced proliferation and decreased apoptosis, whereas its upregulation inhibited proliferation and increased apoptosis. The effects of lubiprostone, a CLCN2 activator, were also investigated. In lubiprostone-treated cells, proliferation was inhibited and apoptosis was increased. The microarray analysis demonstrated that interferon (IFN) signaling-related genes were downregulated in CLCN2-depleted cells. IHC showed the presence of CLCN2 in the cytoplasm and cell membranes of ESCC cells. The prognostic analysis revealed a relationship between weak CLCN2 expression and shorter overall survival., Conclusions: The present results indicate that tumor progression is regulated by CLCN2 through its effects on IFN signaling. Furthermore, weak CLCN2 expression was associated with poorer outcomes in ESCC patients. The present study will contribute to a clearer understanding of the role of CLCN2 as a mediator of ESCC, as well as its use as a biomarker for this cancer., (© 2021. Society of Surgical Oncology.)

Identifying the depth of invasion (DOI) of superficial esophageal squamous cell carcinoma (SESCC) is crucial to determine the indication for endoscopic resection. This retrospective, single-center study aimed to evaluate the diagnostic efficacy of magnifying blue laser imaging (M-BLI) compared with white-light imaging (WLI) or magnifying narrow-band imaging (M-NBI) for identifying the DOI of SESCC. A total of 160 consecutive patients with SESCCs who underwent endoscopic submucosal dissection were enrolled in this study. Still images of the lesion were obtained using WLI, M-BLI and M-NBI prior to endoscopic submucosal dissection. Three endoscopists retrospectively evaluated the DOI using WLI according to non-magnifying findings and using M-BLI and M-NBI images according to the magnifying endoscopic classification of the Japan Esophageal Society. The diagnostic accuracy of each modality was compared using the chi-square test. The DOIs in 160 SESCCs evaluated pathologically were as follows: invasion to the epithelium or lamina propria mucosa in 130, invasion to the lamina muscularis mucosa or submucosa to a depth ≤ 200 μm in 18, and invasion to the submucosa to a depth > 200 μm in 12. The overall diagnostic accuracy rates of WLI, M-BLI, M-NBI, WLI with M-BLI (WLI + M-BLI), and WLI with M-NBI (WLI + M-NBI) were 86.9, 91.2, 90.6, 95.6 and 94.4%, respectively. Significant differences were found between WLI and WLI + M-BLI or WLI + M-NBI (P = 0.006 and P = 0.021, respectively). The concordance of intrapapillary capillary loops between M-BLI and M-NBI was 91.2%. The kappa coefficients for interobserver variability of the three endoscopists for M-BLI and M-NBI were 0.728/0.649/0.792 and 0.729/0.666/0.791, respectively, while those for intraobserver variability were 0.919/0.746/0.778 and 0.736/0.720/0.745, respectively. Similar to M-NBI, M-BLI was useful in predicting the DOI of SESCCs., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Few studies have reported the function and activation mechanism of ANO9 in esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the role of ANO9 in the regulation of tumor progression., Methods: Knockdown experiments with human ESCC cell lines were performed using ANO9 siRNA, and the effects on cell proliferation, the cell cycle, apoptosis, and cellular movement were analyzed. Immunohistochemistry (IHC) analysis was performed on 57 primary tumor samples obtained from ESCC patients., Results: In an in vitro study, depletion of ANO9 reduced cell proliferation, invasion, and migration in KYSE150 and KYSE 790 cells. In the cell cycle analysis, depletion of ANO9 increased the number of cells in G 0 /G 1 arrest. In addition, the knockdown of ANO9 increased apoptosis. The results of the microarray analysis indicated that various centrosome-related genes such as CEP120, CNTRL, and SPAST were up- or downregulated in ANO9-depleted KYSE150 cells. The IHC results showed that high expression of ANO9 was associated with poor prognosis., Conclusions: The results of the current study suggest that ANO9 regulates the cell cycle via centrosome-related genes in ESCC.

Background: Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC)., Methods: Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples., Results: TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients., Conclusion: The present results suggest that TRPV2 regulates cancer progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.

The volume-regulated anion channel is composed of leucine-rich repeat-containing protein A (LRRC8A) and is activated by hypotonic conditions to implement the process of regulatory volume decrease. The role of LRRC8A in regulating genes related to progression of esophageal squamous cell carcinoma (ESCC) was investigated, as well as the prognostic significance of LRRC8A expression in this tumor. Knockdown experiments were conducted using ESCC cell lines and LRRC8A siRNA to assess the influence of this protein on tumor function. In addition, the gene expression profile of ESCC was determined by microarray analysis. Immunohistochemistry was performed on 64 primary tumor samples from ESCC patients receiving radical esophagectomy. It was found that depletion of LRRC8A decreased cell proliferation and migration and also promoted apoptosis. Microarray data demonstrated G 1 /S checkpoint regulation and up-regulation or down-regulation of phosphatidylinositol 3-kinase/AKT signaling, matrix metalloproteinase, and integrin signaling-related genes (including p21, p27, MMP1, and ITGAV) in LRRC8A-depleted cells. Immunohistochemistry showed that LRRC8A expression was related to the pathologic N and T stage categories, and strong LRRC8A expression was correlated with a worse prognosis of ESCC. These findings indicate that LRRC8A modulates tumor progression by influencing cell cycle, apoptosis, and migration, providing new insights into its function as an effector or biomarker of ESCC., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The patient was a 69-year-old woman.Upper gastrointestinal endoscopy showed a protruding tumor in the mid-thoracic esophagus, and biopsy revealed small cell carcinoma in November 2012. Four courses of neoadjuvant chemotherapy comprising CDDP and CPT-11 were administered, and radical resection was performed in March 2013.I n March 2014, chest computed tomography revealed the recurrence of mediastinal lymph nodes; thus, we administered chemoradiotherapy comprising 5- FU and CDDP, and the size of the recurrent tumors decreased.However, in February 2015, positron emission tomographycomputed tomography revealed liver metastases.Therefore, we switched to a new chemotherapy regimen containing CDDP and VP-16.Although the treatment was very effective and the liver metastases significantly decreased in size, it was discontinued after 9 courses owing to neurotoxicity.Next, 7 courses of chemotherapy comprising amrubicin, which is administered for treating small cell lung carcinoma, were administered, which suppressed tumor growth for approximately 8 months.However, the tumor then re-grew.Chemotherapy comprising S-1 was administered; however, the tumor gradually progressed.The patient died 51 months after the initial treatment.

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S-transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Undernutrition and sarcopenia are associated with a higher incidence of chemotherapy-related toxicity and a poor prognosis in several kinds of cancer, but the impact of sarcopenia on the outcomes of chemotherapy for esophageal cancer remains unclear. Thus, the purpose of this retrospective study was to investigate whether sarcopenia affects the efficacy and toxicities of chemotherapy for advanced esophageal cancer patients. Data were collected from 31 esophageal cancer patients who underwent neo-adjuvant chemotherapy followed by surgery. Body composition was assessed at the start of chemotherapy by bioelectrical impedance analysis, and outcomes of chemotherapy were compared between sarcopenic and non-sarcopenic groups. Of the 31 patients, sarcopenia was observed in 16 (51.6%). The incidence of toxicities was not different between the two groups. However, as for pathologic response, a good therapeutic effect (Grade 2 or higher) was more common in the non-sarcopenic group than in the sarcopenic group (53.3% vs. 25.0%). Multivariate analysis showed that sarcopenia was an independent predictor of poor pathological response (odds ratio 8.02; P = 0.037). The results of this study suggest the potential utility of sarcopenia assessment in neoadjuvant patient selection strategies.

Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.

Background: Transient receptor potential melastatin 7 (TRPM7) is a Mg 2+ /Ca 2+ -permeable channel with kinase activity and is expressed in many solid tumor types. However, it has not been evaluated in esophageal squamous cell carcinoma (ESCC). The aim of this study was to evaluate the prognostic impact of TRPM7 in ESCC and to determine the role of TRPM7 in proliferation, migration and invasion of ESCC., Materials and Methods: Immunohistochemistry of TRPM7 for 52 primary tumor samples obtained from patients with ESCC undergoing esophagectomy was performed. Expression of TRPM7 in human ESCC cell lines was analyzed by real-time polymerase chain reaction (PCR). Knockdown experiments were conducted with TRPM7 siRNA, and the effect on cell proliferation, migration and invasion was analyzed., Results: Immunohistochemical staining showed that TRPM7 was found in the cytoplasm of carcinoma cells, and that expression was an independent prognostic factor of good postoperative survival. Suppression of TRPM7 expression with TRPM7-siRNA increased the proliferation, migration and invasion of TE5 ESCC cells., Conclusion: The expression of TRPM7 has an impact on the prognosis of patients with ESCC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Na+/H+ exchanger 1 (NHE1) is a plasma membrane transporter that controls intracellular pH and regulates apoptosis and invasion in various cancer cells. However, the function of NHE1 in esophageal squamous cell carcinoma (ESCC) cells and the relationship between the expression of NHE1 and prognosis of ESCC remain unclear. We found that the knockdown of NHE1 in ESCC cells inhibited apoptosis and promoted cell proliferation, migration, and invasion and showed increases in Snail, β-catenin, and activation of PI3K-AKT signaling, which was consistent with the results obtained from microarrays. Microarrays results suggested that the knockdown of NHE1 suppressed Notch signaling pathway. An immunohistochemical investigation of 61 primary ESCC samples revealed that NHE1 was expressed at higher levels in well-differentiated tumors. The 5-year survival rate was poorer in the NHE1 low group (57.0%) than in the NHE1 high group (82.8%). Multivariate analyses revealed that the weak expression of NHE1 was associated with shorter postoperative survival (hazard ratio 3.570, 95% CI 1.291-11.484, p = 0.0135).We herein demonstrated that the suppression of NHE1 in ESCC may enhance malignant potential by mediating PI3K-AKT signaling and EMT via Notch signaling, and may be related to a poor prognosis in patients with ESCC.

Aim: To investigate the role of Na(+)/K(+)/2Cl(-) cotransporter 1 (NKCC1) in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC)., Methods: An immunohistochemical analysis was performed on 68 primary tumor samples obtained from ESCC patients that underwent esophagectomy. NKCC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted using NKCC1 small interfering RNA, and the effects on cell cycle progression were analyzed. The gene expression profiles of cells were analyzed by microarray analysis., Results: Immunohistochemical staining showed that NKCC1 was primarily found in the cytoplasm of carcinoma cells and that its expression was related to the histological degree of differentiation of SCC. NKCC1 was highly expressed in KYSE170 cells. Depletion of NKCC1 in these cells inhibited cell proliferation via G2/M phase arrest. Microarray analysis identified 2527 genes with altered expression levels in NKCC1depleted KYSE170. Pathway analysis showed that the top-ranked canonical pathway was the G2/M DNA damage checkpoint regulation pathway, which involves MAD2L1, DTL, BLM, CDC20, BRCA1, and E2F5., Conclusion: These results suggest that the expression of NKCC1 in ESCC may affect the G2/M checkpoint and may be related to the degree of histological differentiation of SCCs. We have provided a deeper understanding of the role of NKCC1 as a mediator and/or a biomarker in ESCC.

Background: xCT is a component of the cysteine/glutamate transporter, which plays a key role in glutathione synthesis. The objectives of the present study were to investigate the role of xCT in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC)., Methods: xCT expression in human ESCC cell lines was analyzed by Western blotting and immunofluorescent staining. Knockdown experiments were conducted with xCT siRNA, and the effect on cell cycle was analyzed. The cells' gene expression profiles were analyzed by microarray analysis. An immunohistochemical analysis of 70 primary tumor samples obtained from ESCC patients that had undergone esophagectomy was performed., Results: xCT was highly expressed in TE13 and KYSE170 cells. In these cells, the knockdown of xCT using siRNA inhibited G1-S phase progression. Microarray analysis identified 1652 genes whose expression levels in TE13 cells were altered by the knockdown of xCT. Pathway analysis showed that the top-ranked canonical pathway was the G1/S checkpoint regulation pathway, which involves TP53INP1, CDKN1A, CyclinD1/cdk4, and E2F5. Immunohistochemical staining showed that xCT is mainly found in the nuclei of carcinoma cells, and that its expression is an independent prognostic factor., Conclusions: These observations suggest that the expression of xCT in ESCC cells might affect the G1/S checkpoint and impact on the prognosis of ESCC patients. As a result, we have a deeper understanding of the role played by xCT as a mediator and/or biomarker in ESCC.

Background: Aquaporins (AQPs) are water channel proteins that facilitate transcellular water movements. Recent studies have shown that AQP5 is expressed in various cancers, and plays a role in tumor progression. However, its expression and role in esophageal squamous cell carcinoma (ESCC) have not been investigated. We examined the pathophysiologic role of AQP5 in cell proliferation and survival, and also investigated its expression and effects on the prognosis of ESCC patients., Methods: AQP5 expression in human ESCC cell lines was analyzed by Western blot testing. Knockdown experiments with AQP5 siRNA were conducted, and the effects on cell proliferation, cell cycle progression, and cell survival were analyzed. The cells' gene expression profiles were analyzed by microarray analysis. Immunohistochemistry of AQP5 for 68 primary tumor samples obtained from ESCC patients undergoing esophagectomy was performed., Results: AQP5 expression was high in TE2 and TE5 cells. In these cells, the knockdown of AQP5 using siRNA inhibited cell proliferation and G1-S phase progression, and induced apoptosis. The AQP5 siRNA transfected TE5 cells showed significant increase in p21 and decrease in CCND1 mRNA expression, respectively. The expression pattern of AQP5 and p21 protein was sharply contrasted, but AQP5 and CCND1 protein expression showed a similar pattern in ESCC tissue. These findings agree with the microarray results. Immunohistochemical staining of 68 ESCC patients showed the AQP5 expression is associated with tumor size, histological type, and tumor recurrence., Conclusion: The AQP5 expression in ESCC cells may affect cell proliferation and survival, and impact on the prognosis of ESCC patients.

The objectives of the present study were to investigate the role of K-Cl cotransporter 3 (KCC3) in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT) was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN), and the survival rate of patients with a CN > MT score was lower than that of patients with a CN ≤ MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

Background: E2F Transcription Factor 5 Protein (E2F5) is considered to act primarily as a transcriptional repressor in the cell cycle. However, its expression and role in esophageal squamous cell carcinoma (ESCC) have not been investigated. We examined whether the expression of E2F5 is related to the clinicopathological features and prognosis of patients with ESCC., Materials and Methods: The expression of E2F5 was analyzed by immunohistochemistry in 64 primary tumor samples obtained from patients with ESCC who had undergone curative esophagectomy between 1998 and 2009. According to the expression of E2F5 in tumor cells, cases were divided into E2F5-positive (27 cases) and -negative groups (37 cases). The relationship of various clinicopathological features and prognosis with the E2F5 status, were analyzed., Results: In the clinicopathological analysis, the proportion of poorly-differentiated tumors was significantly higher in the E2F5-positive group than in the E2F5-negative group (p=0.027). The 5-year survival rate of the E2F5-positive group was 39.3%, which was significantly poorer than that of the E2F5-negative group (83.8%) (p=0.006). In multivariate analysis, the expression of E2F5 was one of the most important independent prognostic factors after radical esophagectomy., Conclusion: The expression of E2F5 in ESCC may be correlated with a worse prognosis of patients with ESCC.

Background: Although p21 is an important component that regulates cell-cycle progression, no consensus has been reached about its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated its prognostic significance and correlation with cyclin-D1 (CCND1) expression in ESCC., Materials and Methods: The p21 labeling index (LI) was calculated by immunohistochemistry for 69 primary tumor samples obtained from patients with ESCC who had undergone curative esophagectomy, and correlations between p21 LI and various clinicopathological features, prognosis, and CCND1 LI were studied., Results: The p21 LI of these tumors ranged from 2.0% to 57.0% (median=28.4%, mean±SD=27.3% ± 13.0). p21 LI was positively correlated with CCND1 LI. When patients were divided into two groups using a p21 LI cut-off value of 30%, the 5-year survival rate of patients with p21 LI of ≥ 30% was 80.0%, which was significantly higher than that of patients with p21 LI of <30% (55.5%). Furthermore, when patients were divided into four groups according to p21 and CCND1 expression, the 5-year survival rate of patients with p21 LI of <30% and CCND1 LI of ≥ 45% was the lowest (44.4%). Multivariate analysis demonstrated that venous invasion, lymphatic invasion, and p21 LI were independent prognostic factors., Conclusion: Our results indicate that p21 LI is correlated with CCND1 LI and can be used as an independent prognostic factor for patients with ESCC following selection of a suitable cut-off value.

Background: Adaptor proteins, with multimodular structures, can participate in the regulation of various cellular functions. A novel adaptor protein XB130 has been implicated as a substrate and regulator of tyrosine kinase-mediated signaling and in controlling cell proliferation and apoptosis in thyroid and lung cancer cells. However, its expression and role in gastrointestinal cancer have not been investigated. We sought to determine the role of XB130 in cell cycle progression of esophageal squamous cell carcinoma (ESCC) cells and to examine its expression and effects on the prognosis of patients with ESCC., Methods: Expression of XB130 in human ESCC cell lines was analyzed by Western blot testing and immunofluorescent staining. Knockdown experiments with XB130 small interfering RNA (siRNA) were conducted, and the effect on cell cycle progression was analyzed. Immunohistochemistry of XB130 for 52 primary tumor samples obtained from patients with ESCC undergoing esophagectomy was performed., Results: XB130 was highly expressed in TE2, TE5, and TE9 cells. In these cells, knockdown of XB130 with siRNA inhibited G1-S phase progression and increased the expression of p21, the cyclin-dependent kinase inhibitor. Immunohistochemistry showed that 71.2% of the patients expressed XB130 in the nuclei and/or cytoplasm of the ESCC cells. Further, nuclear expression of XB130 was an independent prognostic factor of postoperative survival., Conclusions: These observations suggest that the expression of XB130 in ESCC cells may affect cell cycle progression and impact prognosis of patients with ESCC. A deeper understanding of XB130 as a mediator and/or biomarker in ESCC is needed.

Background: The immunohistochemical staining of phospho-histone H3 (PHH3) has recently been reported to predict the prognosis of different tumors. However, it has not been evaluated in esophageal squamous cell carcinoma (ESCC). The aim of this study was to evaluate the prognostic impact of PHH3 in ESCC., Materials and Methods: The number of anti-phophohistone H3-positive nuclei [i.e. PHH3 mitotic index (MI)] was calculated by immunohistochemistry of 50 primary tumor samples obtained from patients with ESCC who underwent curative esophagectomy., Results: The PHH3 MI per 10 high-power fields ranged from 1 to 72 (median=15.5). When the patients were divided into two groups using a cut-off value of 10, the 5-year survival rate of the patients with PHH3 MI ≤10 was significantly higher than that of patients with PHH3 MI >10. Multivariate analysis indicated PHH3 MI to be an independent prognostic factor., Conclusion: The expression of PHH3 impacts the prognosis of patients with ESCC.