Stage Nasopharyngeal Carcinoma Research Articles

Cytoplasmic p27 is a novel prognostic biomarker and oncogenic protein for nasopharyngeal carcinoma

Cytoplasmic p27 plays an important role in regulating the cell cycle. Recent studies have revealed p27 protein translocation from the nucleus to the cytoplasm in many tumour cells. The aim of this study was to investigate the role and molecular mechanisms of cytoplasmic p27 in the progression of nasopharyngeal carcinoma (NPC) and to explore its prognostic value. We found increased cytoplasmic p27 expression by immunohistochemistry in NPC tissues, and its expression level was significantly correlated with the T classification and TNM clinical stage of NPC. The survival rate was significantly lower for NPC patients with cytoplasmic p27 immunopositivity than for NPC patients with cytoplasmic p27 immunonegativity, and cytoplasmic p27 was an independent risk factor that affected the prognosis of patients with NPC. Cytoplasmic p27 promoted the proliferation, cell cycle progression, migration, and invasion of NPC cells, increased Bim-1 and Twist1 protein levels, and decreased RhoA-GTP level. Collectively, these findings suggest that cytoplasmic relocalization of p27 is involved in the pathogenesis of NPC and is closely related to the unfavourable prognosis of patients with NPC. Therefore, cytoplasmic p27 might be a useful prognostic factor and potential therapeutic target for patients with NPC.

Prognostic role of pre-treatment serum albumin in patients with nasopharyngeal carcinoma: A meta-analysis and systematic review.

Pre-treatment serum albumin (ALB) is a novel index that was identified in recent years and is considered to be closely related to the prognosis of nasopharyngeal carcinoma (NPC). However, the association between ALB and NPC remains controversial. To assess the prognostic significance of pre-treatment serum ALB in patients with NPC. A systematic review and meta-analysis. We searched PubMed, the Cochrane Library and the Web of Science for studies published up to August 2018. The keywords used were related to albumin, nasopharyngeal carcinoma and prognosis. We extracted the following data from all included studies: author, publication year, country, cancer centre, time points of randomisation, sample size, mean or median age, gender, TNM stage of NPC, cut-off value of pre-treatment serum albumin, number of high-grade cases and duration of follow-up. Then, we generated the pooled hazard ratios (HR) for overall survival (OS) and distant metastasis-free survival (DMFS) to perform this meta-analysis. Ten studies comprising 7339 cases were included. Lower pre-treatment serum ALB levels were significantly associated with worse OS (HR=1.32, 95% CI 1.17-1.48) and DMFS (HR=1.40, 95% CI 1.08-1.80). In general, our findings were further verified in the subgroup analyses based on three features, including cancer stage, cut-off value and analysis type. A decreased level of pre-treatment serum albumin implies a poor prognosis and can be detected to define the risk stratification of NPC patients.

COMPARISON OF CYTHOCROME P450 FAMILY 2 SUBFAMILY A POLYPEPTYDE 6 (CYP2A6) GENE POLYMORPHISM PROPORTION ON EARLY AND ADVANCED STAGE OF UNDIFFERENTIATED TYPE NASOPHARYNGEAL CARCINOMA IN BALINESE

Introduction
 Nasopharyngeal carcinoma (NPC) is a malignancy derived from epithelial cells lining the nasopharynx. The etiology of nasopharyngeal carcinoma is multifactorial. One of the risk factors is CYP2A6 gene polymorphism which causes nitrosamines are not metabolized, leading to DNA change that could trigger cancer.
 Objectives
 The purpose of this study is to know the association of CYP2A6 gene polymorphism and clinical stage of undifferentiated type of NPC
 Material and Method
 This is a cross sectional analytic study. The sample in this study were 80 nasopharyngeal carcinoma patients whose treated in ENT-HN department of Sanglah General Hospital between 2017 - 2018. The collected data consist of subject’s characteristic and CYP2A6 gene polymorphisms identified by the PCR-RFLP technique.
 Results
 The probability of CYP2A6 gene polymorphism in the undifferentiated type of NPC in the Balinese tribe is 3.125 times greater in advanced stage than early stage. Based on multivariate analysis, there was a statistically significant association between CYP2A6 gene polymorphism and clinical stage of undifferentiated type NPC in Balinese with p value = 0,0048 (p < 0,05).
 Conclusion
 There is association between CYP2A6 gene polymorphism and clinical stage of undifferentiated type NPC in Balinese tribe.

Soluble MICA and anti-MICA Antibodies as Biomarkers of Nasopharyngeal Carcinoma Disease

ABSTRACT The MHC class I chain-related molecule A (MICA) is a ligand for the activating natural killer (NK) cell receptor NKG2D. A part from its genetic diversity, MICA is characterized by the presence of membrane-bound and soluble isoform (sMICA) and by the propensity to elicit antibody-mediated allogeneicity (MICA Abs). Altogether such properties are important in the cancer setting. Here, we investigated whether MICA polymorphism, serum level of sMICA and MICA antibodies (Abs) may influence nasopharyngeal carcinoma (NPC) risk. 274 NPC naïve of treatment patients and 275 healthy individuals, all originating from Tunisia were included and genotyped. Among them, 160 sera from patients and 51 from controls were analyzed for the sMICA level by ELISA and were tested for the presence of MICA Abs by Luminex assay. The statistical analysis showed that: (1) we extend and confer our previous finding concerning Val/Val association with risk of NPC (p = .02, OR = 1.56; 95%CI [1.12–2.11]). (2) The higher level of sMICA characterized patients advanced stage of the disease. (3) The 18 (78%) of patients having MICA Abs exhibit all a non-advanced stage of the tumor extension at presentation. MICA129 Met /Val, sMICA and MICA Abs could be potential biomarkers of prediction, the diverse staging of NPC and hence prognostic and treatment.

Effects of hepatitis B virus infection and antiviral therapy on the clinical prognosis of nasopharyngeal carcinoma.

PurposeTo investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis.MethodsWe conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow‐ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log‐rank test and Cox regression analysis.ResultsAmong the 876 participants, 106 (12.1%) patients were HBV‐infected patients. The hepatitis B surface antigen‐positive [HBsAg(+)] group had a lower CD4+ T cell count than the HBsAg(−) group (P = .048). Among patients with stage I/II NPC, 5‐year overall survival (OS), disease‐free survival (DFS), relapse‐free survival, and distant metastasis‐free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(−) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P = .017, .018, and .004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5‐year DMFS existed between the antivirus (90.0%) and no‐antivirus groups (70.0%) (P = .043).ConclusionsHepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(−) group. Anti‐HBV treatment may improve the prognosis of HBV‐infected NPC patients.

The long-term survival of patients with III-IVb stage nasopharyngeal carcinoma treated with IMRT with or without Nimotuzumab: a propensity score-matched analysis

BackgroundTo assess the efficacy of Nimotuzumab in combination with first-line chemoradiotherapy treatment in Chinese patients with primary III-IVb stage nasopharyngeal carcinoma.MethodsPatients with primary locoregionally advanced nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin-based chemotherapy between January 2008 and December 2013 at a single institution were retrospectively reviewed. Group A received at least 6 doses of Nimotuzumab, while Group B did not receive Nimotuzumab. A propensity score matching method was used to match patients from each group in a 1:3 ratio.ResultsIn total, 730 eligible patients were propensity matched, with 184 patients in Group A and 546 patients in Group B. Significant differences were not observed in the patient and tumor characteristics between Group A and Group B. At a median follow-up of 74.78 months (range 3.53–117.83 months), locoregional recurrence, distant failure and death were observed in 10.68, 11.10 and 16.03% of all patients, respectively. The estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in the Group A versus Group B were 85.34% versus 89.79% (P = 0.156), 93.09% versus 85.61% (P = 0.012), 79.96% versus 77.99% (P = 0.117) and 88.91% versus 78.30% (P = 0.006), respectively.ConclusionsThis nimotuzumab-containing regimen resulted in improved long-term survival of III-IVb stage NPC patients and warrants further prospective evaluation.

In vivo three-dimensional evaluation of tumour hypoxia in nasopharyngeal carcinomas using FMT-CT and MSOT

PurposeAccurate evaluation of hypoxia is particularly important in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The aim of this study was to propose a novel imaging strategy for quantitative three-dimensional (3D) evaluation of hypoxia in a small animal model of NPC.MethodsA carbonic anhydrase IX (CAIX)-specific molecular probe (CAIX-800) was developed for imaging of hypoxia. Mouse models of subcutaneous, orthotopic, and spontaneous lymph node metastasis from NPC (5 mice per group) were established to assess the imaging strategy. A multi-modality imaging method that consisted of a hybrid combination of fluorescence molecular tomography-computed tomography (FMT-CT) and multispectral optoacoustic tomography (MSOT) was used for 3D quantitative evaluation of tumour hypoxia. Magnetic resonance imaging, histological examination, and immunohistochemical analysis were used as references for comparison and validation.ResultsIn the early stage of NPC (2 weeks after implantation), FMT-CT enabled precise 3D localisation of the hypoxia biomarker with high sensitivity. At the advanced stage (6 weeks after implantation), MSOT allowed multispectral analysis of the biomarker and haemoglobin molecules with high resolution. The combination of high sensitivity and high resolution from FMT-CT and MSOT could not only detect hypoxia in small-sized NPCs but also visualise the heterogeneity of hypoxia in 3D.ConclusionsIntegration of FMT-CT and MSOT could allow comprehensive and quantifiable evaluation of hypoxia in NPC. These findings may potentially benefit patients with NPC undergoing radiotherapy in the future.Graphical abstractA novel multimodality imaging strategy for three-dimensional evaluation of tumour hypoxia in an orthotopic model of nasopharyngeal carcinoma.

290O - Long-term results of phase II trial of reduced modified clinical target volume in low-risk nasopharyngeal carcinoma treated with intensity modulated radiotherapy

BackgroundIntensity modulated radiation therapy (IMRT) is the standard of care for nasopharyngeal carcinoma (NPC). Part of the IMRT quality assurance process involves accurate target volume delineation, which is crucial for local control and survival. Current practice utilizes a uniform contouring method for clinical target volume (CTV) for all stages of NPC. Here, we conducted a single-arm phase 2 trial investigating the tumor control rates of reduced CTV margins and corresponding doses in low-risk, early-stage NPC. MethodsPatients with biopsy-proven stage I-IIb (6th UICC/AJCC) NPC were enrolled. All patients were treated with IMRT alone. Two CTVs (CTV1 [high risk] and CTV2 [low risk]) were outlined; CTV1 was defined by grossly identified tumour (on MRI or CT) plus 5-mm margin (3-mm posteriorly); CTV2 was CTV1 plus 5-mm margin (3-mm posteriorly). 60 Gy and 50–54 Gy in 30 fractions were prescribed to CTV1 and CTV2, respectively. Primary end-point was locoregional recurrence free survival (LRRFS). ResultsFrom May 2001 to August 2006, 103 patients were recruited; all patients completed IMRT as planned (time duration 39-61 days). At a median follow-up of 12.6 years, five patients developed locoregional failures; of which one was in-field, and four were regional recurrence (two in-field and two marginal). 10-year LRRFS, distant metastasis free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 95.0% and 94.1%, 94.0% and 91.1%, respectively. The most common grade 1-2 late toxicities included subcutaneous fibrosis (79.6%), hearing loss (53.4%) and skin dystrophy (43.2%); grade 3 included subcutaneous fibrosis (2.9%) and hearing loss (2.9%); and no grade 4 late toxicity. ConclusionsReduced CTV margins and corresponding doses results in optimal longterm tumour control, with minimal late adverse events. Clinical trial identificationNCT03839602. Legal entity responsible for the studyProf. Chong Zhao. FundingHas not received any funding. DisclosureM.L.K. Chua: Honoraria (self), Advisory / Consultancy: Janssen, Astellas, Varian, Ferring Singapore and AstraZeneca; Research grant / Funding (institution): Ferring Singapore, GenomeDx Biosciences, Varian, MedLever. All other authors have declared no conflicts of interest.

Maintenance chemotherapy using S-1 following definitive chemoradiotherapy in patients with N3 nasopharyngeal carcinoma

BackgroundPatients with N3 stage nasopharyngeal carcinoma (NPC) are at high risk for treatment failure. This study aims to assess the efficacy of maintenance chemotherapy (MC) using S-1 (MC-S1), a novel oral fluoropyrimidine agent, following definitive chemoradiotherapy (CRT) using intensity-modulated radiotherapy (IMRT) in patients with N3 nasopharyngeal carcinoma (N3-NPC).MethodsA retrospective review was conducted for all N3-NPC treated with CRT with MC (CRT-MC) or without MC (CRT-non-MC) during 2014–2016. Toxicities with MC were recorded. Overall survival (OS), locoregional failure-free survival (LFFS) and distant metastasis free survival (DMFS) were compared between CRT-MC vs. CRT-non-MC cohorts.ResultsA total of 130 N3 patients were identified, of whom 21 (16.2%) were treated with CRT-MC, and 109 (83.8%) with CRT-non-MC. Patient characteristics did not significantly differ between the CRT-MC and CRT-non-MC groups, with the exception of the number of cycles of neoadjuvant chemotherapy. Following IMRT 69 patients achieved a complete response (CR) (CRT-MC: 10; CRT-non-MC: 59), 61 had a partial response (PR) (11 vs. 50), and none maintained stable disease (SD) or developed progression of disease (PD). After a median follow-up of 41 months for surviving patients, a significant differences in OS (76.3% vs. 95.2%, p = 0.046) and DMFS (70.3% vs. 90.5%, p = 0.043) but not LFFS (84.9% vs. 100%, p = 0.091) at 3 years were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leucopenia, fatigue, neutropenia, anorexia and nausea were the common but not severe (grade 1–2) toxicities of MC.ConclusionsUsing MC-S1 in N3-NPC patients following IMRT achieved superior survival to the CRT-non-MC patients. The toxicities of MC-S1 were mild and tolerable. Further clinical trials are required to evaluate the efficacy of MC-S1 in N3-NPC patients.

Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)‐associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost‐effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI‐W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI‐W 121 bp and ebv‐miR‐BART7‐3p were validated. Hsa‐miR‐29a‐3p and hsa‐miR‐103a‐3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI‐W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.

1141P - Long-term results of phase II trial of reduced modified clinical target volume in low-risk nasopharyngeal carcinoma treated with intensity modulated radiotherapy

BackgroundIntensity modulated radiation therapy (IMRT) is the standard of care for nasopharyngeal carcinoma (NPC). Part of the IMRT quality assurance process involves accurate target volume delineation, which is crucial for local control and survival. Current practice utilizes a uniform contouring method for clinical target volume (CTV) for all stages of NPC. Here, we conducted a single-arm phase 2 trial investigating the tumor control rates of reduced CTV margins and corresponding doses in low-risk, early-stage NPC. MethodsPatients with biopsy-proven stage I-IIb (6th UICC/AJCC) NPC were enrolled. All patients were treated with IMRT alone. Two CTVs (CTV1 [high risk] and CTV2 [low risk]) were outlined; CTV1 was defined by grossly identified tumour (on MRI or CT) plus 5-mm margin (3-mm posteriorly); CTV2 was CTV1 plus 5-mm margin (3-mm posteriorly). 60Gy and 50–54Gy in 30 fractions were prescribed to CTV1 and CTV2, respectively. Primary end-point was locoregional recurrence free survival (LRRFS). ResultsFrom May 2001 to August 2006, 103 patients were recruited; all patients completed IMRT as planned (time duration 39-61 days). At a median follow-up of 12.6 years, five patients developed locoregional failures; of which one was in-field, and four were regional recurrence (two in-field and two marginal). 10-year LRRFS, distant metastasis free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 95.0% and 94.1%, 94.0% and 91.1%, respectively. The most common grade 1-2 late toxicities included subcutaneous fibrosis (79.6%), hearing loss (53.4%) and skin dystrophy (43.2%); grade 3 included subcutaneous fibrosis (2.9%) and hearing loss (2.9%); and no grade 4 late toxicity. ConclusionsReduced CTV margins and corresponding doses results in optimal long-term tumour control, with minimal late adverse events. Clinical trial identificationNCT03839602. Legal entity responsible for the studyChong Zhao. FundingNational Natural Science Foundation of China [No. 81872469]; Science and Technology Project of Guangdong Province [No. 2014A020212433]. DisclosureM.L.K. Chua: Honoraria (institution), Advisory / Consultancy: Janssen, Astellas, Varian, Ferring Singapore and AstraZeneca; Research grant / Funding (institution), Structured research agreement/Research funding - Ferring Singapore, GenomeDx Biosciences, Varian, MedLever.: Ferring Singapore, GenomeDx Biosciences, Varian, MedLever. All other authors have declared no conflicts of interest.

THE RELATION OF EBNA-1 AND EGFR EXPRESSION SCREENING FROM ADVANCED STAGE UNDIFFERENTIATED NASOPHARYNGEAL CANCER

Introduction:
 Nasopharyngeal carcinoma (NPC) is a lymphoepithelial malignancy of the nasopharynx, one of the etiologies is the infection of Epstein–Barr virus in undifferentiated type of nasopharyngeal carcinoma. The Epstein-Barr virus Nucleus Antigen-1 (EBNA-1) is Epstein–Barr virus-encoded proteins as regulatory virus transcription. Epithelial Growth Factor Receptor (EGFR) consist of a single polypeptide chain of amino acid, ErbB members, tyrosine kinase receptor, a transmembrane glycoprotein encoded by gen location in the short arms of a chromosome and overexpression in epithelial tumors. EGFR plays a central role in signal transduction pathways which regulate key cellular functions in epithelial malignancies. and may also present in NPC.
 Objective:
 To investigate this relation of expression patterns of EBNA-1 and EGFR in a histological type of undifferentiated nasopharyngeal carcinoma.
 Method:
 Observational, analytical study with a cross-sectional method of 34 formalin-fixed within inclusion criteria are EBNA-1 and positive staining of EGFR expression (30 patients) and exclusion criteria of negative staining of EGFR (4 patients). All biopsy samples work with paraffin embedded and resulted in hematoxylin-eosin undifferentiated histological types of the advanced stage in nasopharyngeal carcinoma. EBNA-1 and EGFR expression used immunohistochemistry staining.
 Result:
 EBNA-1 and EGFR expression level were detection and correlated with the advanced stadium of nasopharyngeal undifferentiated carcinoma.
 Conclusion: 
 EBNA-1 is significantly related to EGFR expression in the advanced stadium of undifferentiated nasopharyngeal carcinoma. Overexpression of EGFR is mostly found in advanced NPC but not in all ages. Male is dominated and overall age below 55 years old. Screening of EGFR with immunohistochemistry is highly considered before anti-EGFR treatment

EPIDERMAL GROWTH FACTOR RECEPTOR EXPRESSION IN NON-KERATINIZED NASOPHARYNGEAL CARCINOMA SUBTYPE AT PADANG

Introduction: 
 Patients with nasopharyngeal carcinoma have a poor prognosis, there are several factors that cause it to happen, one of the existing therapeutic response has been inadequate. Expression of Epidermal Growth Factor Receptor (EGFR) has been used as a biological marker targeted therapy in nasopharyngeal carcinoma. Histopathologic subtype tumors also determine the prognosis of patients with nasopharyngeal carcinoma.
 Objective: 
 The aim of the study to determine between the expression of epidermal growth factor receptor between non-keratinized differentiated and undifferentiated subtypes in nasopharyngeal carcinoma and correlation with their clinical stage. Study design, Cross-sectional comparative study. Place and duration study, Department of Otorhinolaryngology, Department of Pathology Anatomy in Dr. M. Djamil Hospital, Padang and Department of Pathology Anatomy in Gajah Mada University, between May 2015 until October 2015
 Material and methods: 
 We included 36 samples paraffin blocks of nasopharyngeal carcinoma biopsy, respectively 18 paraffin blocks are non-keratinized differentiated and 18 non-keratinized undifferentiated nasopharyngeal carcinoma subtypes. Each sample examined EGFR expression by immunohistochemical staining methods.
 Results: 
 There were positive EGFR expression results in all sample as 69.4%. Expression of EGFR positive non-keratinized differentiated subtypes in nasopharyngeal carcinoma as 77.8% and undifferentiated subtype as 61.6%. There are no significant differences of EGFR expression between non keratinized differentiated and undifferentiated subtypes nasopharyngeal carcinoma (P>0.05). There are no significant differences of EGFR expression between new and advanced stage nasopharyngeal carcinoma (P>0.05).
 Conclusion: 
 There were no significant differences of EGFR expression between non-keratinized differentiated and non-keratinized undifferentiated subtypes in nasopharyngeal carcinoma. Analysis of the study also showed no significant differences of EGFR expression based on the clinical stage nasopharyngeal carcinoma.

OVEREXPRESSION VASCULAR ENDOTHELIAL GROWTH FACTOR IN NASOPHARYNGEAL CARCINOMA WITH UNDIFFERENTIATED CARCINOMA TYPE IN ADVANCED STAGE

Introduction:
 Nasopharyngeal Carcinoma (NPC) is a malignancy that tends to diagnosed at an advanced stage with low survival and prognosis rate. One of the factors that may play a role in progressivity and metastasis of tumor is overexpression of vascular endothelial growth factor (VEGF), which is a key role in tumor angiogenesis.
 Objective:
 This study aims to learn the expression of VEGF in NPC with Undifferentiated Carcinoma type and to learn the association pf VEGF Expression with tumor stage of NPC
 Method:
 This is a cross-sectional study performed in ENT-HNS Department of ENT-HNS of Udayana University/Sanglah Hospital. The sample was collected by consecutive nonprobability sampling, starting from January 2016. NPC patients underwent Histopathologic examination from a nasopharyngeal biopsy. The result is Undifferentiated Carcinoma. VEGF expression analyzed by red-brown stained cytoplasm. Data were analyzed by Spearman's Correlation Test Chi-Square test, and Paired Sample t-Test.
 Result:
 VEGF positive Expression was found in 27 of 28 (96.4%) Undifferentiated Carcinoma type of NPC cases. VEGF overexpression was found in 23 of 28 (82.4%) Undifferentiated Carcinoma type of NPC cases.There is significant correlation found between tumor stage and VEGF expression (p<0.05).
 Conclusion: 
 From the research, it could conclude that there is significant correlation between tumor stage and VEGF Expression.

Preliminary analysis of the factors influencing the secondary external auditory canal carcinoma of nasopharyngeal cancer

Objective In order to investigate the clinical features and influence factors for incidence in patients with radiation-induced external auditory canal carcinoma (RIEACC). Methods The nasopharyngeal carcinoma (NPC) 16 patients who were diagnosised RIEACC after radiotherapy in the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from January 1990 to December 2017 were retrospectively analysis. The influence factors analysis were used Logistic regression analysis. Results Univariate analysis showed that age, somking history, family history of cancer and NPC stage were the influencing factors. Multi-factor logistic regression analysis showed that age, family history of cancer and NPC stage were independent risk factors. Conclusions RIEACC is rare complication of NPC patients received radiotherapy, which is also a multifactorial outcome. Age, family history of cancer and NPC stage is preliminary the main influencing factor. Although RIEACC has a low incidence, its malignancy should be highly vigilant. Key words: Nasopharyngeal neoplasms/radiotherapy; Radiation-induced external auditory canal carcinoma; Influencing factors

Contrast-enhanced Ultrasound in evaluating of angiogenesis and tumor staging of nasopharyngeal carcinoma in nude mice.

ObjectiveTo explore the use of Contrast-enhanced Ultrasound (CEUS) in evaluating angiogenesis in a xenograft nasopharyngeal carcinoma (NPC) model in nude mice and the evolution of CEUS parameters according to the growth of NPC.MethodsNude mice were divided into three groups according to experiments conducted at various times from tumor implantation (8 mice/group; group A: 4 weeks from implantation; group B:6 weeks from implantation; group C:8 weeks from implantation). CNE-2 cells were transplanted in 24 nude mice and CEUS evaluations of the tumors were performed at 4, 6 or 8 weeks from implantation. CEUS parametric perfusion images and pathological findings were recorded. R version 3.4.4 software was used to analyze the CEUS parameters and pathological findings.ResultsOne-way anova analysis indicated statistically significant differences among the three groups with the parameters of peak intensity (PI) (p<0.001), area wash in (AWI) (p<0.001), area wash out (AWO) (p<0.001) and tumor volumes (p<0.001).Pearson correlation coefficient analysis indicated that microvessel density (MVD) was correlated with tumor volume (r = 0.644, p = 0.001), PI (r = 0.904, p<0.0001), AWI (r = 0.547, p = 0.008) and AWO (r = 0.744, P<0.0001). Tumor volume was correlated with MVD (r = 0.644, p = 0.001), PI (r = 0.625, p = 0.002), AWI (r = 0.528, p = 0.012) and AWO (r = 0.784, p<0.001). The percentage of necrosis in histological sections was correlated with the percentage of CEUS unperfused area (r = 0.446,p = 0.038). Spearman rank correlation coefficient analysis indicated that vascular endothelial growth factor (VEGF) was correlated with PI (r = 0.462, P = 0.032). Welch t test indicated PI, AWI and AWO parameters were significantly lower than that of kidneys (p<0.001, p = 0.009, p = 0.005).ConclusionsThe CEUS parameters PI, AWI and AWO indirectly reflect the MVD and the tumor volume in our model of subcutaneous transplanted NPC in nude mice, providing precious information on angiogenesis and tumor growth. VEGF may play a role in promoting angiogenesis of NPC.

Low expression of ZMYND8 correlates with aggressive features and poor prognosis in nasopharyngeal carcinoma.

PurposeZMYND8 is closely correlated with cancerous proliferation and invasiveness. However, its prognostic value has not been estimated in a nasopharyngeal carcinoma (NPC). The purpose of this study was to elucidate the status of ZMYND8 expression and its prognostic significance in NPCs.MethodsThe status of ZMYND8 expression was investigated by immunohistochemistry for NPC samples in the study. The cutoff value of ZMYND8 expression was confirmed in NPCs using ROC-curve analysis. Correlations between ZMYND8 expression and clinicopathological variables and patient prognosis were analyzed by various statistical methods.ResultsOur study showed that low expression of ZMYND8 strongly correlated with late T stage in NPCs (P<0.05). Kaplan–Meier survival analysis revealed a significant association between low ZMYND8 expression and worse overall survival (P<0.05). Most importantly, Cox regression analysis confirmed ZMYND8 expression in NPC could be an independent prognostic factor.ConclusionLow expression of ZMYND8 could be of importance, due to its displaying more aggressive behavior in NPC. Therefore, ZMYND8 expression might serve as an independent prediction factor in patients with NPCs.

Clinical significance of circulating tumor cells and their expression of cyclooxygenase-2 in patients with nasopharyngeal carcinoma.

To explore the expression of circulating tumor cells (CTCs) and cyclooxygenase-2 (COX-2) in CTCs and to assess their association with clinical parameters and treatment. Peripheral blood samples from 50 patients with nasopharyngeal carcinoma (NPC) were included. We applied advanced CanPatrolTM CTC enrichment technique and in situ hybridization assay to isolate, identify, and classify CTCs and COX-2 in CTCs. Epstein-Barr virus DNA was detected by Real Time-quantitative PCR (RT-qPCR). No CTCs were identified in ten healthy volunteers (100%). Of the total patients, 48 (96%) had positive CTCs counts and 36 (72%) had positive mesenchymal CTCs counts before treatment. CTCs cells were highly expressed in different NPC stages, and the positive ratio of mesenchymal CTCs in stage IV was higher than that in other stages. The proportion of mesenchymal cells was higher expressed in metastasis patients. The expression of COX-2 was different in different types of CTCs. The positivity of COX-2 in CTCs was higher in stage IV patients than that in stage II and stage III patients. Decreased mesenchymal CTCs and that express COX-2 indicated a favorable curative effect in NPC patients. The positivity of mesenchymal CTCs and COX-2 was higher in EBV DNA positive patients compared with EBV DNA negative patients (p<0.05). Meanwhile, the mean number of CTCs, mesenchymal CTCs, CTCs that express COX-2, hybrid CTCs that express COX-2 and mesenchymal CTCs that express COX-2 was significantly higher in the EBV DNA positive patients than negative patients before treatment (p<0.05). CTCs and their expression of COX-2 were correlated with NPC clinical characteristics, and have a relation with Epstein-Barr virus DNA. Decreased mesenchymal CTCs and that express COX-2 indicated a favorable curative effect in NPC patients.

Associations between environmental factors and serological Epstein‐Barr virus antibodies in patients with nasopharyngeal carcinoma in South China

Epstein‐Barr virus (EBV) reactivation, reflected by aberrantly increased levels of various serological antibodies, has been suggested to be an early indicator of nasopharyngeal carcinoma (NPC) onset and progression. We have previously suggested that certain lifestyle and dietary factors were associated with elevated serological levels of the antibody against various EBV antigens namely VCA, Zta, EBNA1, and oral EBV DNA loads among healthy population. It remains unclear whether these potential environmental factors would also influence EBV serological antibodies in NPC patients. We conducted an epidemiological study to evaluate the associations between such environmental factors and EBV antibody levels among 1701 NPC patients in South China. Pretreatment serums were collected and examined for VCA‐IgA and EA‐IgA by immunoenzymatic assays and antienzyme rate (AER) of EBV DNase‐specific neutralizing antibody. We found that consumption of Canton‐style herbal tea was significantly correlated with increased serological antibody levels of VCA‐IgA and EA‐IgA, with adjusted ORs of 1.35 (95% CI: 1.03‐1.76) and 1.32 (95% CI: 1.01‐1.73), respectively, in the weekly intake frequency stratum, while not related to AER of EBV DNase‐specific neutralizing antibody. Smoking was found to be not only an apparent risk factor for higher antibody levels of AER in stage III‐IV patients (OR = 1.60, 95% CI: 1.11‐2.30), but also associated closely with NPC stage at diagnosis (OR = 2.17, 95% CI: 1.47‐3.22), with dose‐response effects. In conclusion, we found consumption of Canton‐style herbal tea and cigarette smoking were in positive associations with elevated EBV antibodies in NPC patients, which may be of public health significance for the primary prevention of EBV‐associated diseases especially NPC.

Clinical application of diffusion-weighted magnetic resonance imaging in radiotherapy for nasopharyngeal carcinoma.

To explore the clinical application of diffusion-weighted magnetic resonance imaging (DWI) in nasopharyngeal carcinoma (NPC) diagnosis, detection of lymph node metastasis, radiotherapy and prognosis. Twenty patients with diagnosed NPC in an early stage of radiotherapy were enrolled in our department between May 2010 and May 2013. T1 and T2 weighted magnetic resonance imaging and DWI of the nasopharynx and neck were performed 1 week before radiotherapy, during radiotherapy at a dose of 60 Gy, and 1 month after radiotherapy. Pertinent measurements and related data were recorded. In comparison with that before radiotherapy, the ADC value of the nasopharyngeal primary lesion increased significantly during radiotherapy at a dose of 60 Gy and at 1 month after radiotherapy (F = 187.160, P = 0.000). When the dose of radiotherapy reached 60 Gy, the DWI signals from both the neck and the retropharyngeal lymph nodes were significantly lower than those before radiotherapy. DWI can be used for sensitive and accurate diagnosis of lymph node metastasis in the neck and retropharyngeal space, monitoring of the radiotherapy effect in early stages of NPC and development of new medical treatment strategies.