• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10299-10306
• /
• 2015

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.4123-4126
• /
• 2015

Background: Carcinoma of the esophagus is associated with significant morbidity and mortality. The most common subtype is squamous cell carcinoma (SCC). In the past three decades, the incidence of SCC has been reported to be decreasing whereas esophageal adenocarcinoma (AC) is increasing. This study assessed the trend of esophageal cancer in Brunei Darussalam over a three decades period. Materials and Methods: The National Cancer registry was searched for esophageal cancers from 1986 to 2012. Data on age, gender, racial groups (Malays, Chinese, Indigenous and foreign nationals) and histology type were collected. The rate (ASR) and Age Specific Incidence rate (ASIR) were calculated. Results: The predominant tumor type was SCC which accounted for 89% of all esophageal cancer. The gender ratio was 2.25: 1 (male: female) and the mean age at diagnosis was $66.9{\pm}12.9$ years, significantly younger for esophageal AC ($57.2{\pm}16.0$) compared to SCC ($68.1{\pm}12.0$, p<0.05), and among the foreign nationals (p<0.05 for trend). The proportions of SCC among all esophageal cancers in the various racial groups were: Malays (87.8%), Chinese (100%), Indigenous (100%) and foreign nationals (20%). None of the Chinese and Indigenous groups were diagnosed with esophageal AC. The overall ASR for esophageal cancer was 2.1/100,000; 2.0/100,000 for SCC with a declining trend and 0.17/100,000 for esophageal AC, without any trend observed. Among the two major racial groups; the Chinese has higher ASR (3.42/100,000) compared to the Malays (ASR 0.95/100,000). Conclusions: SCC is the predominant tumor type of esophageal cancer in Brunei Darussalam and more common among the Chinese. There was a declining trend in the incidence of SCC but not for esophageal AC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.2
• /
• pp.797-802
• /
• 2015

Background: The purpose of this study was to prospectively evaluate the predictive value of perfusion computed tomography (CT) for response of local advanced esophageal carcinoma to radiotherapy and chemotherapy. Materials and Methods: Before any treatment, forty-three local advanced esophageal squamous cell carcinomas were prospectively evaluated by perfusion scan with 16-row CT from June 2009 to January 2012. Perfusion parameters, including perfusion (BF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Seventeen cases received definitive radiotherapy and 26 received concurrent chemo-radiotherapy. The response was evaluated by CT scan and esophagography. Differences in perfusion parameters between responders and non-responders were analyzed, and ROCs were used to assess predictive value of the baseline parameters for treatment response. Results: There were 25 responders (R) and 18 non-responders (NR). Responders showed significantly higher BF (R:34.1 ml/100g/min vs NR: 25.0 ml/100g/min, p=0.001), BV (23.2 ml/100g vs 18.3 ml/100g, p=0.009) and PED (32.5 HU vs 28.32HU, P=0.003) than non-responders. But the baseline TTP (R: 38.2s vs NR: 44.10s, p=0.172) had no difference in the two groups. For baseline BF, a threshold of 36.1 ml/100g/min achieved a sensitivity of 56%, and a specificity of 94.4% for detection of clinical responders from non-responders. Conclusions: The results suggest that the perfusion CT can provide some helpful information for identifying tumors that may respond to radio-chemotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.1
• /
• pp.271-274
• /
• 2015

Background: To explore vascular endothelial growth factor C (VEGF-C) and VEGF-D expression and its correlation with lymph node metastasis in esophageal squamous cell cancer (ESCC) tissue. Materials and Methods: Immunohistochemical methods were applied to detect the levels of VEGF-C and VEGF-D expression in 64 surgicall removal ESCC tissues, tissues adjacent to cancer and normal tissues, and the relationship between VEGF-C and VEGF-D expression and lymph node metastasis was analyzed. Results: Both VEGF-C and VEGF-D were expressed by varying degrees in esophageal cancer tissue, the tissue adjacent to cancer and normal tissue, and the positive expression rate went down successively. The positive expression rates of VEGF-C (59.4%) and VEGF-D (43.8%) in esophageal cancer tissue were significantly higher than in the tissue adjacent to cancer (34.4%, 15.6%) and normal tissue (20.3%, 12.5%), respectively, in which significant differences were manifested (p<0.01). Positive expression rates of VEGF-C and VEGF-D in esophageal cancers with lymph node metastasis were markedly higher than without such metastasis (p<0.01), while those in the tissue with TNM staging I~II were markedly lower than that with TNM staging III~IV (p<0.01). Conclusions: Both VEGF-C and VEGF-D are highly expressed in ESCC tissue, which may be related to the lymph node metastasis of cancer cells. Hence, VEGF-C and VEGF-D can be clinically considered as important reference indexes of lymph node metastasis in esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.2
• /
• pp.647-651
• /
• 2012

Aim: An epidemiological study was conducted based on an esophageal cancer patient's cohort to investigate the association of folate intake and MTHFR C677T polymorphism with the prognosis of esophageal cancer in a Chinese population. Methods: 167 patients aged 37-75 years who had histological confirmed diagnosis of esophageal squamous cell cancer were collected from Jan. 2006 to Jan. 2008. MTHFR genotypes at the C677T site were analyzed by PCR-based RFLP methods, and the folate intake was computed by multiplying the food intake (in grams) and the folate content (per gram) of food in our questionnaire. Results: We found associations between the prognosis of esophageal cancer and smoking status, T and N stages. Individuals carrying the MTHFR 677CT and TT genotypes showed a shorter survival time than with the CC genotype, with adjusted HRs (95% CI) of 1.20 (0.56-2.15) and 2.29 (1.30-4.28), respectively. Similarly, those carrying MTHFR 677T allele had a 1.86-fold risk of death. A higher folate concentration showed a significant decreased risk of death, with an HR (95% CI) of 0.45 (0.18-0.87). Individuals with high folate intake and the MTHFR 677CC genotype showed a significant decreased risk of esophageal cancer (0.43, 0.25-0.89).Conclusion: Our findings supports the hypothesis that high folate intake and active MTHFR C677T polymorphism may exert protective roles in the prognosis of esophageal cancer in the Chinese population.

• Korean Journal of Bronchoesophagology
• /
• v.17 no.1
• /
• pp.23-28
• /
• 2011

Diagnosis of early esophageal cancer has become more frequent as a result of improved endoscopic technology, surveillance programmes, and increasing experience and awareness on the part of endoscopists. In early esophageal cancer, squamous cell carcinoma and early adenocarcinoma must be managed differently because they have different origins, pathogenesis. and clinical characteristics. The current treatment options vary widely, from extended resection with lymphadenectomy to endoscopic mucosal resection (EMR) or ablation. None of these treatment options can be recommended universally. Instead, an individualized strategy should be based on the depth of tumor infiltration into the mucosa or submucosa, the presence or absence of lymph node metastases, the multicentricity of tumor growth, the length of the segment of intestinal metaplasia, and comorbidities of the patient. EMR has become increasingly important, both as a diagnostic tool for the staging of esophageal carcinomas and as a method of carrying out definitive treatment when the cancer meets certain criteria in which the risk of lymph-node metastasis is negligible. EMR may be sufficient in a subset of patients who have m1 or m2 squamous cell carcinoma and in patients who have isolated foci of high-grade intraepithelial neoplasia or mucosal cancer.

• Journal of Chest Surgery
• /
• v.54 no.6
• /
• pp.454-459
• /
• 2021

According to statistics from 2017, esophageal cancer is the fifteenth most common cancer and the eleventh most common cause of cancer-related death in Korea. The most common pathology is esophageal squamous cell carcinoma. Moreover, the incidence of esophageal cancer has been gradually decreasing in Korea, and the percentage of early-stage cases has gradually increased to the point that it is higher than that of other countries. The 5-year relative survival rate has improved over time. Approximately 800 esophagectomy procedures are performed annually. Using a cut-off number of 21 cases per 2 years to define high-volume centers, it was found that 70% of esophagectomies were performed by a few high-volume centers. Unfortunately, there is no nationwide registry or database on esophageal cancer and esophagectomy in Korea. Efforts to establish a nationwide database on esophageal cancer and esophagectomy should be made.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2851-2857
• /
• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.4
• /
• pp.1261-1266
• /
• 2012

Introduction: HPV has been found repeatedly in esophageal squamous cell carcinoma (ESCC) tissues. However, reported detection rates of HPV DNA in these tumors have varied markedly. Differences in detection methods, sample types, and geographic regions of sample origin have been suggested as potential causes of variation. We have reported that infection of HPV DNA in ESCC tumors depends on anatomical sites of esophagus of the patients from Mazandaran, north of Iran. Materials and Methods: HPV DNA was examined in 46 upper, 69 middle and 62 lower third anatomical sites of esophageal squamous cell carcinoma specimens collected from Mazandaran province in north Iran, near the Caspian Littoral as a region with high incidence of ESCC. HPV L1 DNA was detected using Qualitative Real time PCR and MY09/MY11 primers. Results: 28.3% of upper, 29% of middle and 25.8% of lower third of ESCC samples were positive for HPV DNA. 13.6% for males and 14.1% for females were HPV positive in all samples. Conclusions: HPV infection is about one third of ESCC in this area. Findings in this study increase the possibility that HPV is involved in esophageal carcinogenesis. Further investigation with a larger sample size is necessary.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.16
• /
• pp.7161-7165
• /
• 2015

Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer in the north east of India. The present study concerned the prevalence of human papilloma virus (HPV) in the ESCC in north eastern India and its impact on response to chemotherapy. Materials and Methods: p16 expression, a surrogate marker for HPV infection was assessed in 101 pre-treatment biopsies of locally advanced ESCC, reported from a comprehensive cancer centre in north east India, using immunohistochemistry. All patients received neo-adjuvant chemotherapy. Response was assessed clinically and histopathologically with attention to p16 expression. Results: p16 was expressed in 22% of ESCC (22 out of 101) and was more prevalent in patients who were more than 45 years of age (P=0.048). p16 positive tumors appeared more commonly in the upper 2/3 of the thoracic esophagus (18 in 22). Nine of the 22 (41%) p16 positive tumors achieved pathologic complete response following neo-adjuvant chemotherapy (P=0.008). There was a trend towards reduced mortality in this group (P=0.048). Some 9 of the 20 (45%) patients who achieved pathologic complete response were p16 positive. Conclusions: Expression of p16 in ESCC correlates with higher rate of pathologic complete remission in patients undergoing neo adjuvant chemotherapy and could be a predictive marker for response assessment.