The cadherin–catenin complex in nasopharyngeal carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze β-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. β-Catenin and E-cadherin expression were examined in 18 nasopharyngeal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clinical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. β-catenin was detected in membrane and cytoplasm in all cases of nasopharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, β-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carcinoma tissues. E-cadherin expression was associated with β-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic β-catenin in nasopharyngeal carcinoma may impair cell–cell adhesion, promoting invasive behavior and a metastatic tumor phenotype.     

The incidence of Epstein–Barr virus in nasopharyngeal carcinoma of Jordanian patients

Aim of this study was to investigate the incidence of Epstein–Barr virus (EBV) in patients diagnosed with undifferentiated nasopharyngeal carcinoma (UNPC) from the Northern Province of Jordan. All cases diagnosed with UNPC at King Abdullah University Hospital, Irbid, Jordan, between the years 1991 and 2009 inclusive were examined. Clinical data including age, gender, mode of presentation, site of biopsy were retrieved from pathology reports. In situ hybridization for (EBV)—EBERs was performed on cases with available paraffin blocks. Correlation between the different clinical variables and results of in situ hybridization was performed. There were 49 cases diagnosed with UNPC, only 39 specimens were available and studied. The median age of presentation was 41 years (range 9–70 years). Bimodal age distribution was noted, the first peak between 15 and 19 years of age and second between 60 and 64 years of age. Males were slightly more commonly affected than females. Cervical lymph node enlargement was the most common mode of presentation, followed by nasal obstruction. Biopsies were obtained primarily from the posterior nasal space, followed by cervical lymph node. Positive staining for EBERs by in situ hybridization was seen in 92.3% of the cases examined. There was no difference in detection rate between males and females or adults and pediatrics. All cases obtained from posterior nasal space were positive. The three negative cases were from biopsies obtained from cervical lymph nodes, which was statistically significant (P value <0.05). Nasopharyngeal carcinoma in Jordan is seen in both children and adults. It is associated with EBV infection in most, but not all cases. Posterior nasal space shows a more consistent staining for EBERs than cervical lymph nodes. The presence of other association with UNPC including cigarette smoking could possibly explain the cases with negative association.     

Frequency of Epstein–Barr virus and human papilloma virus in patients with nasopharyngeal carcinoma

European Archives of Oto-Rhino-Laryngology - Nasopharyngeal cancer is a type of malignancy originating from the epithelial cells lining the nasopharynx. In genetic and environmental factors,...     

Neutrophil–lymphocyte ratio as a new predictive and prognostic factor at the hearing loss of diabetic patients

Diabetes mellitus (DM) is a systemic inflammatory disease. Sensorineural hearing loss (SNHL) is seen more frequently in diabetic patients and it is believed that vascular complications of DM may be the cause of SNHL via inflammation. Neutrophil-to-lymphocyte ratio (NLR) was defined as a novel-potential marker to determine inflammation. We aimed to investigate the relationship between NLR levels and SNHL in diabetic patients using high-frequency audiometry (8–16 kHz) for the first time. The study included 58 patients diagnosed with DM. The control group was composed of 45 age–sex–BMI–matched healthy subjects. An automated blood cell counter was used for NLR measurements. The hearing assessments of the patients were carried out by Interacoustics Clinical Audiometer AC 40 device. The mean NLR values of the patients were significantly higher than the control group (p = 0.015). Speech recognition threshold values were higher and the speech discrimination values were lower in patients (p = 0.002, p < 0.001), respectively. Pure tone average of the patients at 500, 1,000, 2,000 Hz frequencies was divided into two groups (group 1 >25 dB and group 2 <25 dB). NLR levels of the diabetic patients with >25 dB were higher than the other diabetics (p = 0.007). In conclusion, while diabetic patients are evaluating, audiologic assessments of these patients should be performed because they are at more risk of SNHL and NLR may be considered as a predictive and prognostic marker of hearing loss or its beginning in these patients as a useful and reliable marker without any cost.     

Combining Epstein–Barr virus antibodies for early detection of nasopharyngeal carcinoma: A meta-analysis

ObjectiveEpstein–Barr virus-related antibody seromarkers including VCA-IgA, EA-IgA, EBNA1-IgA, and Rta-IgG are used as markers for the detection of nasopharyngeal carcinoma (NPC). This meta-analysis was conducted to evaluate the diagnostic performance of their use in combined assays.MethodsComputerized searching of five electronic databases, supplemented by manual searching methods, was performed to identify pertinent articles. Diagnostic accuracy parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC), were calculated with corresponding 95% confidence intervals (CIs).ResultsTwenty-one studies with 4753 NPC cases and 31875 non-NPC controls were included. The pooled sensitivities for VCA-IgA+EA-IgA, VCA-IgA+EBNA1-IgA, VCA-IgA+Rta-IgG, and VCA-IgA+ EA-IgA+Rta-IgG were 0.89, 0.93, 0.94, and 0.94, respectively. Pooled specificities were 0.89, 0.88, 0.90, and 0.95, respectively. The PLRs were 8.1, 7.6, 9.4, and 17.4, respectively. Pooled NLRs were 0.12, 0.08, 0.07, and 0.07, respectively. Pooled DORs were 66, 95, 135, and 261, respectively. Pooled AUCs were 0.94, 0.96, 0.97, and 0.94, respectively.ConclusionThese four combined assays based on EBV-related antibodies show diagnostic accuracy. The three-marker assay of VCA-IgA, EA IgA, and Rta-IgG has the best performance. Given the aspect of cost-benefit, VCA-IgA combined with EBNA1-IgA or Rta-IgG could become the preferred serodiagnostic strategy for NPC screening and early diagnosis.     

The evaluation of pretreatment neutrophil–lymphocyte ratio and derived neutrophil–lymphocyte ratio in patients with laryngeal neoplasms

IntroductionSystemic inflammatory biomarkers are promising predictive and prognostic factors for solid cancers. The neutrophil–lymphocyte ratio and derived neutrophil–lymphocyte ratio are used to predict inflammation and used as biomarker in several malignancies.ObjectiveThe purpose of this study was to demonstrate the diagnostic, predictive and prognostic role of neutrophil–lymphocyte ratio and derived neutrophil–lymphocyte ratio in patients with laryngeal neoplasms.MethodsA retrospective study was conducted on medical records involving 229 patients with benign, premalignant and malignant laryngeal neoplasms between 2002 and 2015. The diagnostic, predictive and prognostic role of neutrophil–lymphocyte ratio and derived neutrophil–lymphocyte ratio were evaluated using uni– and multivariate analysis.ResultsThe neutrophil–lymphocyte ratio and derived neutrophil–lymphocyte ratio were not statistically different between patients with benign, premalignant and malignant laryngeal neoplasms. Both neutrophil–lymphocyte ratio and derived neutrophil–lymphocyte ratio were predictive factors for stage, lymph node metastasis, and distant metastasis. Patients with high neutrophil–lymphocyte ratio value (≥4) had a poor prognosis when compared with patients with low neutrophil–lymphocyte ratio value (5 year, Overall Survival: 69.0% vs. 31.1%, p < 0.001; 5 year, disease free survival: 70.0% vs. 32.7%, p ? 0.001; 5 year, locoregional recurrence free survival: 69.7% vs. 32.0%, p < 0.001). Furthermore, neutrophil–lymphocyte ratio was an independent prognostic factor for 5 year: Overall survival (HR = 2.396; 95% CI 1.408–4.077; p = 0.001), Disease free survival (HR = 2.246; 95% CI 1.322–3.816; p = 0.006) and locoregional recurrence free survival (HR = 2.210; 95% CI 1.301–3.753; p = 0.003).ConclusionPretreatment neutrophil–lymphocyte ratio is a useful and reliable predictive and prognostic biomarker for patients with laryngeal carcinoma.     

Serologic biomarkers of Epstein–Barr virus correlate with TNM classification according to the seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma

This study aimed to investigate the association between Epstein–Barr virus (EBV)-related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA-IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0–1.85) in Stage I, 1.32 (0–3.51) in Stage II, 3.33 (0–4.30) in Stage III, 3.83 (2.85–4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation.     

The nucleotide polymorphisms within the Epstein–Barr virus C and Q promoters from nasopharyngeal carcinoma affect transcriptional activity in vitro

Epstein–Barr virus (EBV) is a ubiquitous human gamma herpesvirus that is associated with Burkitt’s lymphoma (BL), gastric carcinoma, nasopharyngeal carcinoma (NPC), and NK/T-cell lymphoma. Two viral promoters, Cp and Qp, are important for EBV latent infection. The latency Cp, which is used in primary infection, drives expression of the full spectrum of EBV nuclear antigens. Qp is active in EBV-associated tumors and drives the latency I/II expression pattern. In this study, we determined nucleotides polymorphisms in the Cp and Qp promoter regions in peripheral blood mononuclear cells (PBMCs) from Cantonese healthy carriers and in biopsies of NPC, nasal NK/T lymphoma, BL, and gastric carcinoma. The sequence changes of −12G>T and +69 C>T in Cp and −197 G>A and +1 G>C in Qp were frequently identified in NPC. Transient transfection studies using luciferase gene reporters revealed a significant reduction (57.11%) in gene expression from the Cp +69T variant and increased expression (43.5%) from the Qp +1C variant compared to the prototype, suggesting that these sequence variations affect promoter activity. Our results indicate that the nucleotides polymorphisms in Cp and Qp occur frequently in NPC and might contribute to the oncogenesis of EBV.     

PKCα promotes local advancement via its dual roles in nasopharyngeal carcinoma

Conclusion: In patients with nasopharyngeal carcinoma (NPC), PKCα is linked to local advancement and plays dual roles in tumorigenesis. Moreover, positive PKCα is associated with 2-year overall survival of NPC.

Objective: This study seeks to investigate the role of PKCα to identify different sub-types in NPC.

Methods: PKCα expression levels were detected in a collection of NPC samples. CT and MRI scans of the corresponding patients were used to assess adjacent tissue invasion and lymph node metastasis. The correlation of tumour invasion and PKCα levels was evaluated by statistical analysis. The correlation between expression level of PKCα and 2-year overall survival was analysed by the Kaplan-Meier curves. Moreover, a multivariate Cox proportional hazard regression analysis was used to identify the independent prognostic factors for NPC.

Results: PKCα is linked to the invasion of adjacent tissues, especially in the skull base. However, down-regulation of PKCα is a risk factor for regional lymph node metastasis. The 2-year overall survival of the PKCα negative group is better than that of the PKCα positive group (PKCα negative group 100%, PKCα positive group 88.5%, p?=?0.034). Based on the multivariate Cox proportional hazard regression analysis, age was identified as a risk factor.     

M2-polarized tumour-associated macrophages in stroma correlate with poor prognosis and Epstein–Barr viral infection in nasopharyngeal carcinoma

Objectives: To assess the relationships between CD163 expression, localization of CD163⁺ macrophages, clinicopathological features and prognosis of NPC.

Methods: A total of 110 cases of NPC specimens and 80 cases of nasopharyngitis specimens were analysed for CD163 expression by immunohistochemistry and EBERs expression in situ hybridization.

Results: CD163?+?macrophages in the tumour stroma were positively correlated with the tumour and nodal stage. Higher expression of Epstein–Barr virus-encoded RNAs (EBERs) in the nuclei of tumour cells was associated with higher density of CD163?+?macrophages in the tumour stroma. More importantly, greater infiltration of CD163?+?macrophages in the tumour stroma was associated with poor overall survival (OS) and poor progression-free survival (PFS). Multivariate analysis revealed that the density of CD163⁺?macrophages in the tumour stroma may be an independent risk factor for NPC prognosis.

Conclusions: Increased infiltration of CD163⁺?macrophages in the tumour stroma correlates with worse outcomes and with Epstein–Barr virus (EBV) infection status of tumour cells in nasopharyngeal carcinoma (NPC).     

The value of transmandibular approach to total maxillectomy in the management of T3–T4 carcinoma of the maxillary sinus

Surgical excision of the maxilla either as a primary procedure or after radiotherapy continues to play an important role in the management of carcinoma of the maxillary sinus. A majority of these cancers are seen in T3–T4 stage. Recurrence at the infratemporal fossa has been recognized as a major cause of failure. Although the importance of inclusion of the pterygopalatine fossa in the field of excision has been recognized, there is no uniform approach for en bloc removal of the pterygopalatine fossa. Transmandibular approach has been described for purpose and practiced at the Bangalore Institute of Oncology for the past 8 years with success. This paper presents the technique used, its benefits and the results obtained.     

Activities of γ-glutamyl transpeptidase and erythrocyte glutathione dependent enzymes in nasopharyngeal carcinoma patients and normal controls

Summary Plasma -glutamyltranspeptidase (-GT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in normal and nasopharyngeal carcinoma (NPC) patients. No difference in enzyme activities was observed in the three major races of the Malaysian population, i.e. Malay, Chinese and Indian patients. However, plasma -GT, erythrocyte glutathione S-transferase (GST) and GPx activities were significantly increased in all NPC patients, while GR activity remained unchanged. Patients with elevated plasma -GT activities also had increased GST and GPx activities. Plasma -GT and GPx activities were then found to be affected by treatment. Patients with plasma -GT activity greater than 70 IU/1 had very poor prognoses but patients with decreased -GT activities were found to be in remission.     

Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group

This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51–3.5) and 2.3 (95 % CI 1.72–5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment.     

Occult metastases from T1–T2 supraglottic carcinoma: role of primary tumor localization

The present study was undertaken to evaluate the role of localization on the rate of occult metastasis in early stage supraglottic laryngeal carcinoma. We selected carefully 32 T1–2 clinically N0 patients without epilarynx involvement and 39 T1–2 clinically N0 patients with epilarynx involvement from among patients with supraglottic laryngeal carcinoma. All patients underwent simultaneous unilateral or bilateral neck dissection with laryngeal surgery. The rate of the occult metastases was 3.1% in patients without epilarynx involvement, whereas it was 20.5% in patients with epilarynx involvement. Within the supraglottic larynx, two subregions can be distinguished: the epilarynx and the lower supraglottis. Our results suggest the possibility of omitting elective neck treatment in T1–2N0 supraglottic laryngeal carcinoma without epilarynx involvement. Observation under strict follow-up may be an option to routine neck treatment in T1–2N0 supraglottic laryngeal carcinoma without epilarynx involvement.