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At least 19 recordsLinked to original sources

PubMed2006

Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells.

The Bmi-1 oncoprotein regulates proliferation and oncogenesis in human cells. Its overexpression leads to senescence bypass in human fibroblasts and immortalization of human mammary epithelial cells. In this study, we report that compared with normal nasopharyngeal epithelial cells (NPEC), Bmi-1 is overexpressed in nasopharyngeal carcinoma cell lines. Importantly, Bmi-1 was also found to be overexpressed in 29 of 75 nasopharyngeal carcinoma tumors (38.7%) by immunohistochemical analysis. In contrast to nasopharyngeal carcinoma, there was no detectable expression of Bmi-1 in noncancerous nasopharyngeal epithelium. Moreover, high Bmi-1 expression positively correlated with poor prognosis of nasopharyngeal carcinoma patients. We also report that the overexpression of Bmi-1 leads to bypass of senescence and immortalization of NPECs, which normally express p16(INK4a) and exhibit finite replicative life span. Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16(INK4a) expression. Mutational analysis of Bmi-1 showed that both RING finger and helix-turn-helix domains of it are required for immortalization of NPECs. Our findings suggest that Bmi-1 plays an important role in the development and progression of nasopharyngeal carcinoma, and that Bmi-1 is a valuable marker for assessing the prognosis of nasopharyngeal carcinoma patients. Furthermore, this study provides the first cellular proto-oncogene immortalized nasopharyngeal epithelial cell line, which may serve as a cell model system for studying the mechanisms involved in the tumorigenesis of nasopharyngeal carcinoma.

Biomarkers, Tumor↗

PubMed2003

Screening nasopharyngeal carcinoma by detection of the latent membrane protein 1 (LMP-1) gene with nasopharyngeal swabs.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common head and neck cancer in Taiwan. The goals of the current study were to investigate whether a nasopharyngeal swab technique could provide enough DNA for polymerase chain reaction (PCR) analysis of the Epstein-Barr virus (EBV)-derived latent membrane protein 1 (LMP-1) gene and to determine the feasibility and reliability of diagnosing NPC by detection of LMP-1 in the nasopharynx. METHODS: 320 adults underwent nasopharyngoscopy and nasopharyngeal swab to obtain cells for the LMP-1 PCR assay; some patients also underwent nasopharyngeal biopsy. RESULTS: An amount of DNA that was sufficient for PCR was extracted from 96.3% of the swab samples. By detecting LMP-1 in nasopharyngeal swabs, NPC was diagnosed with a false positive rate of 12.7% (7 of 55 patients), a false negative rate of 1.6% (4 of 253 patients), sensitivity of 87.3% (48 of 55 patients), specificity of 98.4% (249 of 253 patients), a positive predictive value of 92.3% (48 of 52 patients), and a negative predictive value of 97.3% (249/256 patients). NPC was diagnosed by nasopharyngoscopy with a false positive rate of 38% (30 of 79 patients), a false negative rate of 0.4% (1 of 241 patients), sensitivity of 62% (49 of 79 patients), specificity of 99.6% (240 of 241 patients), a positive predictive value of 98% (49 of 50 patients), and a negative predictive value of 88.9% (240 of 270 patients). Only 7 (0.2%) of 256 patients with a diagnosis other than NPC had LMP-1 detected in the nasopharyngeal space. CONCLUSIONS: Detecting EBV genomic LMP-1 by nasopharyngeal swab diagnosed NPC with 87.3% sensitivity and 98.4% specificity. EBV genomic DNA usually is not detected by PCR-based methods in the nasopharyngeal space. Its incidence is estimated to be as low as 0.2% among the general population. The nasopharyngeal swab coupled with PCR-based EBV LMP-1 detection could serve as part of a screening program for high-risk populations.

Antigens, Viral↗

PubMed2003

Identification of tissue-specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray.

Suppression subtractive hybridization (SSH) was performed for isolation of tissue-specific genes in nasopharyngeal epithelial tissue, by use of cDNAs from human adult nasopharyngeal epithelial tissue as tester and mixed cDNAs from esophagus, lung, liver, heart, stomach, spleen, skeletal muscle, kidney, and skin as drivers. Fourteen differentially expressed genes in nasopharyngeal epithelial tissue were obtained. Among these genes, LPLUNC1 and SPLUNC1 were confirmed to be specifically expressed in nasopharyngeal epithelial tissue and the trachea. A novel transcript of SPLUNC1, which we designate NASG, was found. We also combined SSH and cDNA microarray hybridization to identify genes whose expressions were altered in nasopharyngeal carcinoma (NPC). We used NPC cell line HNE1 and primary human embryo nasopharyngeal epithelial cells in one SSH experiment, and NPC biopsies and normal adult nasopharyngeal epithelial tissue in another. Some 1,200 SSH inserts from four subtractive cDNA libraries were arrayed onto nylon membranes by use of robotic printing. Differential gene expression was verified by hybridizing of the membranes with radioactively labeled first-strand cDNA from NPC cell line HNE1, primary human embryo nasopharyngeal epithelial cells, NPC biopsies, and normal adult nasopharyngeal epithelial tissue. Seventeen differentially expressed genes in NPC were obtained. Among these genes, we identified SPLUNC1 and LPLUNC1 to be down-expressed in NPC biopsies (34/48, 33/48).

Adult↗

PubMed1991

Epstein-Barr virus in oropharyngeal and nasopharyngeal secretions of patients with nasopharyngeal carcinoma and control subjects.

The frequency of oropharyngeal excreters of the Epstein-Barr virus among patients with nasopharyngeal carcinoma in Hong Kong was compared with those of healthy adults in Hong Kong and California. 6 (3%) of 177 patients, 11 (12%) of 92 Hong Kong residents, and 20 (15%) of 132 Californians were excreters. The virus was detected in the nasopharyngeal secretion of only 1 of 67 patients and in 2 of 73 healthy adults. No convincing evidence for neutralizing antibody in the throat wash and nasopharyngeal secretions of the patients could be obtained. Epstein-Barr viral gene sequencing could not be detected in the throat washes from 27 patients with nasopharyngeal carcinoma, 8 patients with infectious mononucleosis, and 15 healthy adults and in the nasopharyngeal secretions of 35 patients and 17 controls. We conclude that patients with nasopharyngeal carcinoma are no more likely to be oropharyngeal or nasopharyngeal excreters of the Epstein-Barr virus than healthy adults. One possible explanation for this unexpected finding is that the virus infections in nasopharyngeal carcinoma cells are predominantly nonproductive.

Adolescent↗

PubMed2001

Presence of Epstein-Barr virus latent membrane protein 1 gene in the nasopharyngeal swabs from patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in southeastern China and Taiwan. Early detection of the local disease followed immediately by proper treatment is essential to increase the cure and survival rates. Because every NPC tumor cell carries Epstein-Barr Virus (EBV) genomes, detection of EBV genomic DNA such as latent membrane protein 1 gene (LMP1) might indicate the presence of NPC. We developed a simple and noninvasive technique of nasopharyngeal swabbing to acquire nasopharyngeal cells for detecting the presence of EBV genome. The aim of this study was to investigate the feasibility and reliability of this technique. METHODS: We collected nasopharyngeal cells by means of a nasopharyngeal swabbing technique and detected the presence of EBV LMP1 with polymerase chain reaction (PCR). Thirty-eight swab specimens were obtained from patients with NPC who were newly diagnosed or were just beginning radiotherapy. Two groups of control subjects were recruited, including 20 patients with other head and neck cancers and eight family members of the NPC patients. An additional group of 65 NPC patients were enrolled in the course of regular follow-up after definitive radiotherapy. RESULTS: All of the samples yielded sufficient DNA for PCR amplification. Thirty-six of 38 NPC swab samples were positive for EBV LMP1, and all the control subjects had swab sample results negative for EBV. All five patients with suspected local recurrence exhibited positive EBV test results. CONCLUSIONS: Demonstration of EBV LMP1 in the nasopharyngeal swab specimens detected NPC with a sensitivity of 94.7% and specificity of 100%. This study confirms the reliability and feasibility of nasopharyngeal swab in the predicting and screening of NPC.

Base Sequence↗

PubMed2004

Molecular diagnosis of nasopharyngeal carcinoma: detecting LMP-1 and EBNA by nasopharyngeal swab.

OBJECTIVES: The aim of this study was to investigate the feasibility of molecular diagnosis of nasopharyngeal carcinoma (NPC) by combining nasopharyngeal swab and polymerase chain reaction (PCR) to detect Epstein-Barr virus (EBV) derived latent membrane protein-1 gene (LMP-1) and Epstein-Barr nuclear antigen gene (EBNA). METHODS: 437 adults underwent nasopharyngoscopy, possible biopsy, and nasopharyngeal swab to obtain nasopharyngeal cells for the detection of LMP-1 and EBNA by PCR. RESULTS: By detecting LMP-1 and EBNA in the nasopharyngeal swabs, NPC could be diagnosed with a false-positive rate of 1.7% (6/354), a false-negative rate of 8.6% (6/70), a sensitivity of 91.4% (64/70), a specificity of 98.3% (348/354), positive predictive value of 91.4% (64/70), and negative predictive value of 98.3% (348/354). CONCLUSION: Detecting EBV genomic LMP-1 and EBNA by nasopharyngeal swab verifies NPC with a sensitivity of 91.4% and specificity of 98.3%. The nasopharyngeal swab coupled with PCR based EBV LMP-1 and EBNA detection could serve as a good supplement to pathological diagnosis of NPC.

Adult↗

PubMed1995

[A prospective study on relationship between abnormal nasopharyngeal mucosa and nasopharyngeal carcinoma].

Abnormal nasopharyngeal mucosa was defined as abnormal finding under the examination of nasopharyngoscope. 43541 healthy persons aged 30-64 were observed for 6 years in the high risk area of NPC, by mean of EBV serological and nasopharyngeal cavity examination. The results are as follows. 1. In the high risk area of NPC, abnormal nasopharyngeal mucosa such as follicle hyperplasia and bulge are common in the younger people, especially in the post-roof of the nasopharyngeal cavity. 2. There was no significant difference on statistics between the abnormal and normal groups on the positive rate and GMT of EBV VCA/IgA. Abnormal nasopharyngeal mucosa did not change with the change of VCA/IgA titer. 3. There was significant difference on the prevalence rate of NPC between the abnormal nasopharyngeal mucosa and normal groups except the age, sex factors. There was no confirmation of the abnormal nasopharyngeal mucosa as precancerous lesion.

Adult↗

PubMed1998

[Establishment of partial gene expression map of 7q32 in nasopharyngeal carcinoma and primary culture normal nasopharyngeal epithelial cells].

OBJECTIVE: To establish partial gene expression map of 7q32 in nasopharyngeal carcinoma (NPC) cell line, tissues and primary culture normal nasopharyngeal epithelial cells. METHODS: We detected the expression of 20 ESTs at 7q32 in NPC cell line HNE1,13 NPC biopsies and primary culture normal nasopharyngeal epithelial cells using differential RT PCR and Northern hybridization. RESULTS: 8 ESTs (AA188181, AA13079,N27556, AA031919, N22721, H20825, T91284, AA001936) expressed equally in both of HNE1 and primary culture normal nasopharyngeal epithelial cells; 7 ESTs (T64215, AA025822, R60014,R80002,H06688, R60192,R95096) expressed in neither of them; 3 ESTs (H19830,W72688,AA130630) overexpressed in HNE1 ; and 2 ESTs (AA070437, H90882) overexpressed in primary culture normal nasopharyngeal epithelial cells. W72688 and H19830 each overexpressed in 77%(10/13) of NPC biopsies; AA070437 down-expressed in 30.7% of NPC biopsies. CONCLUSION: Partial gene expression map of 7q32 in nasopharyngeal carcinoma cell line ,tissues and primary culture normal nasopharyngeal epithelial cells has been established. The up-regulation of W72688, H19830 and down-regulation of AA070437 may be related to the occurrence of NPC.

Blotting, Northern↗

PubMed2005

Co-expression of c-kit and stem cell factor in primary and metastatic nasopharyngeal carcinomas and nasopharyngeal epithelium.

Expression of c-kit has been demonstrated in 33% of adult nasopharyngeal carcinomas (NPCs) and in 88% of paediatric NPCs. Patients with tumours expressing c-kit tend to exhibit better survival, but a paracrine/autocrine function for the stem cell factor (SCF)/c-kit system in nasopharyngeal carcinomas has not been reported. This study evaluated the expression of c-kit and SCF by immunohistochemical staining of nasopharyngeal epithelium (NPE) and of primary and metastatic NPCs. In addition, c-kit and SCF expression were studied in HONE-1 NPC cells by immunoprecipitation and western blotting. Expression of c-kit and SCF was detected in 75% and 57% of NPE, respectively, and there was 48% co-expression. In primary NPCs, 86% expressed c-kit, 69% had SCF expression, and there was 67% co-expression. In metastatic NPCs, 76% expressed c-kit, 72% expressed SCF and there was 68% co-expression. Co-expression of c-kit and SCF with tyrosine autophosphorylation of p145(c - kit) was demonstrated in HONE-1 NPC cells. In addition, the expression level of c-kit and its autophosphorylation status was not obviously influenced by the transient co-expression of Epstein-Barr nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1). Co-expression of c-kit and SCF is therefore commonly found in nasopharyngeal epithelium and NPCs, and in HONE-1 NPC cells with autoactivation possibly independent of the co-expression of EBNA1 and LMP1. All of these findings suggest that autoactivation of SCF/c-kit signalling may be a potent regulator of the nasopharyngeal epithelial barrier and of immune function at the nasopharyngeal mucosa surface, and may contribute to the carcinogenesis and progression of NPC. Further molecular analysis is required to evaluate the possibility of treatment with tyrosine kinase inhibitors in NPC, analogous to the treatment of gastrointestinal stromal tumours with STI571.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Resolution of severe sleep-disordered breathing with a nasopharyngeal obturator in 2 cases of nasopharyngeal stenosis complicating uvulopalatopharyngoplasty.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by episodic decrements in airflow due to upper airway obstruction. Uvulopalatopharyngoplasty (UPPP) is a potential therapy for OSAHS. Nasopharyngeal stenosis is a rare complication of UPPP that worsens OSAHS. We report two patients referred for OSAHS worsened by nasopharyngeal stenosis complicating UPPP. Both patients were treated with carbon dioxide laser release of adhesions and placement of a nasopharyngeal obturator. Follow-up polysomnograms demonstrated resolution of OSAHS correlating with subjective resolution of symptoms. Nasopharyngeal stenosis complicating UPPP can be successfully treated with scar removal and nasopharyngeal stenting. Polysomnographic demonstration of the effectiveness of this therapy has not previously been reported. Future questions include duration of nasopharyngeal stenting and timing of follow-up polysomnography.

Carbon Dioxide↗

PubMed2006

Differential expression of Epstein-Barr virus-encoded RNA and several tumor-related genes in various types of nasopharyngeal epithelial lesions and nasopharyngeal carcinoma using tissue microarray analysis.

Studies have revealed that Epstein-Barr virus (EBV) infection, genetic aberration, and environmental factors are of importance in the development of nasopharyngeal carcinoma (NPC), although the definite mechanism remains to be fully elucidated. The aim of our study is to investigate using tissue microarray analysis whether differential expression of EBV-encoded small RNA-1 (EBER-1) and several tumor-related genes were associated with NPC carcinogenesis. Immunohistochemistry and in situ hybridization were performed on tissue microarrays containing 148 NPCs and 164 noncancerous nasopharyngeal epithelia (NPE) with different morphologic features. We found that overexpressions of EBER-1 hybridization signals, p53, p21ras, and bcl-2 proteins and loss expressions of p16 and p27 proteins were significantly increased in NPC tissues compared with normal NPE and hyperplastic NPE (P </= .001). The overexpressions of EBER-1 and p53 (P < .001) and the loss expressions of P16 (P < .001) and P27 (P = .005) were also significantly higher and more frequently observed in NPC than in dysplastic NPE. The positive expression of EBER-1 hybridization signals in NPC had significant associations with overexpressions of p53 (P < .001), p21ras (P = .041), and bcl-2 proteins (P < .001) and loss expression of p16 protein (P = .001). Further analysis confirmed that the abnormal expression of p53, p16, and p27 proteins occurred in the earliest stage of nasopharyngeal epithelial carcinogenesis. In the final logistic regression analysis model, the positive hybridization signals of EBER-1 and the abnormal expression of p53, p16, and p27 proteins were independent contributions for nasopharyngeal carcinogenesis, and EBER-1 was the most significant, independent predictor of nasopharyngeal carcinogenesis (hazard ratio = 13.412, 95% confidence interval 6.179-29.111, P < .001). In conclusion, EBV infection, together with overexpressions of p53, and loss expressions of p16 and p27 proteins are involved in the multistep process of human nasopharyngeal epithelial carcinogenesis.

Adenocarcinoma↗

PubMed1996

Differential expression of EBER1 in nontumor nasopharyngeal biopsies and nontumor component of nasopharyngeal carcinoma.

The close association of Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) is well documented and the expression of EBV-related latent genes has been shown in NPC. Nevertheless, the status of EBV infection in the nontumor epithelial and lymphoid cells is not known. In this study, we detected EBV in the nontumor component of NPC and nontumor nasopharyngeal biopsies by in situ hybridization using digoxigenin-labeled antisense EBER1 oligoprobe in 346 nasopharyngeal biopsies. Latent membrane protein (LMP) and ZEBRA were detected by immunohistochemistry in cases containing EBER1-positive cells. The EBV-positive epithelial and lymphoid cells were identified by immunostains for cytokeratin and lymphoid phenotypes. In the nontumor nasopharyngeal biopsies, 21 (11.7%) of 179 cases had EBV-harboring lymphocytes in the lymphoid tissue, while the overlying mucosa was all negative. LMP was demonstrated in lymphoid cells of 14 (66.7%) of these 21 samples. These EBV-positive lymphocytes were B lymphocytes by combined phenotype study. EBER1-containing metaplastic squamous cells were demonstrated in the overlying mucosa close to the tumor tissue in 14 (8.4%) of 167 NPC samples. In contrast, the respiratory epithelial cells in these cases were all negative. Two (1.2%) of these cases had EBV-positive lymphocytes in the lymphoid stroma. Four of the 346 cases had ZEBRA-positive cells. This study demonstrated that latent infection and, occasionally, active replication of EBV were present in stromal B lymphocytes in nasopharyngeal tissue with and without NPC. EBER1 was found only in the metaplastic squamous cells in the mucosa of nasopharyngeal tissues with NPC, but not in those without NPC.

Adolescent↗

PubMed2001

[Clinical observation of TNF-alpha content in nasopharyngeal secretion of patients with nasopharyngeal carcinoma].

OBJECTIVE: To detect the changes of tumor necrosis factor-alpha (TNF-alpha) in nasopharyngeal secretion of patients with nasopharyngeal carcinoma(NPC). METHOD: The content of TNF-alpha in nasopharyngeal secretion was determined by radioimmunoassay (RIA) in 20 controls, 52 patients with NPC. RESULT: The average concentrations of TNF-alpha were (12.95 +/- 4.62) pmol/L in control group, (33.68 +/- 15.13) pmol/L in NPC group and (64.00 +/- 11.57) pmol/L in NPC with necrosis group. The content of TNF-alpha in nasopharyngeal secretion in control group was lower significantly than that of patients with NPC (P < 0.01). CONCLUSION: The level of TNF-alpha in nasopharyngeal secretion of NPC patients was higher than that of normal subjects. To detect the content of TNF-alpha in nasopharyngeal secretion is a useful test for the study and diagnosis of NPC.

Adult↗

PubMed2006

[Application of EB virus latent membrane protein 1 in nasopharyngeal swab in diagnosis of nasopharyngeal carcinoma].

OBJECTIVE: To investigate the feasibility and reliability of detection of Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) gene by nasopharyngeal swab in the diagnosis of nasopharyngeal carcinoma (NPC). To investigate the distribution of 30 bp deletion variant of LMP-1 gene in the local population. METHOD: Nasopharyngeal cells were collected by nasopharyngeal swab, and then DNA was extracted, which was subsequently confirmed by amplification of sequence of beta-thalassemia gene by polymerase chain reaction (PCR). And sequence of LMP1 was amplified with specific primer to verify the significance of LMP1 in the diagnosis of NPC. RESULT: DNA was obtained from 96.4% nasopharyngeal swab samples, LMP1 was detected in 33 of 36 samples, while 2 of 45 samples from normal control, with sensitivity 91.7%, and specialty 95.6%. 30 bp deletion of LMP1 gene was found in 80.6% of NPC samples, and wild type 11.1%. CONCLUSION: Our study suggests that nasopharyngeal swab could be effective method for gene-detection. As a parameter in diagnosis of NPC, LMP1 gene is maybe superior to EBVCA-IgA. 30 bp deletion of LMP1 oncogene is widespread in NPC patients.

Adult↗

PubMed1997

[No point mutation of the 2.8 kb EcORI fragment of the nasopharyngeal carcinoma transforming gene TX in nasopharyngeal carcinoma].

We have previously cloned a nasopharyngeal carcinoma transforming gene from human nasopharyngeal carcinoma cell line CNE-2 using mouse JB6 cell line as the recipient cells. This transforming gene, designated Tx, exhibits moderate transforming activity upon transfection into JB6 cells. Several lines of evidence indicate that the 2.8 kb EcoRI fragment which lies in the middle of the Tx gene is responsible for the transforming activity. The sequence of the 2.8 kb EcoRI fragment was determined, which showed striking homology with the human immunoglobulin light chain C region gene. Using the modified polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) silver staining technique, we studied the possible point mutations of the nasopharyngeal carcinoma gene Tx in nasopharyngeal carcinoma. No mobility shift was detected in eleven paired cases of nasopharyngeal carcinoma biopsies suggesting that in most cases of nasopharyngeal carcinoma, the Tx gene is not activated via a mode of point mutation. Taken together with the previously obtained results we have found that the Tx gene is not activated by gene rearrangement or gene amplification. Therefore, we consider that the Tx gene may have been activated by its interaction with other regulatory factors.

Carcinoma, Squamous Cell↗

PubMed2001

A comparison of nasopharyngeal endoscopy and lateral cephalometric radiography in the diagnosis of nasopharyngeal airway obstruction.

Two auxiliary methods of diagnosing nasopharyngeal airway obstruction were compared. Cephalometric radiography and nasopharyngeal videoendoscopy were evaluated for efficacy in terms of reproducibility and validity. Thirty orthodontic patients (7 to 12 years of age) seeking otorhinolaryngologic treatment for mouth breathing, or mouth and nose breathing, had nasopharyngeal endoscopy and radiographic examinations performed on the same day. Two otorhinolaryngologists analyzed the results. Nasopharyngeal endoscopy was more reliable in identifying all the obstructive nasopharyngeal processes. Endoscopy obtained kappa index scores of almost perfect agreement for diagnosis of posterior nasal septum deviation, of substantial agreement for anterior nasal septum deviation and lower turbinate hypertrophy, and of moderate agreement for middle turbinate hypertrophy. Lateral cephalometric radiography obtained scores of perfect agreement for imaging hypertrophy of the middle turbinate, of almost perfect agreement for imaging hypertrophy of the posterior portion of the inferior turbinate, and of substantial agreement for imaging hypertrophy of the inferior turbinate. Radiographic diagnoses of hypertrophy of the middle and lower turbinates exhibited high sensitivity and low specificity when compared with diagnoses by nasopharyngeal endoscopy.

Cephalometry↗

PubMed2003

Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from patients with mucosal recurrent nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in southeastern China and Taiwan. Early detection of the local disease followed by timely and appropriate treatment is essential to increasing cure and survival rates. Detection of Epstein-Barr virus (EBV) genomic DNA, such as the latent membrane protein 1 gene (LMP-1), in patients postirradiation during follow-up may indicate mucosal recurrence. METHODS: Seventy-one patients with NPC underwent serial nasopharyngeal swabs for LMP-1 polymerase chain reaction assay before, during, and after irradiation. All of patients achieved a complete disease remission of the LMP-1 gene after irradiation that lasted for at least 6 months. RESULTS: The median LMP-1 disease remission time after the beginning of irradiation was 4.3 weeks. Patients with early LMP-1 disease remission (</= 4 weeks after the beginning of irradiation) and delayed LMP-1 disease remission (> 4 weeks) had 3-year local control rates of 93.5% and 76.9%, respectively (P = 0.0529). The LMP-1 gene was detected again (reexpression of LMP-1 [re-LMP-1]) in 10 patients after irradiation with at least 6 months of follow-up. Nine of 10 patients (90%) in the re-LMP-1 positive group and 2 of 61 patients (3.3%) in the re-LMP-1 negative group developed local recurrence. Mucosal recurrence developed in nine patients, and all displayed re-LMP-1. By detecting re-LMP-1 using nasopharyngeal swabs, mucosal recurrence was diagnosed with a sensitivity of 100% (9 of 9 patients) and a specificity of 98.4% (61 of 62 patients). The 3-year overall survival rate, the disease free survival rate for the entire group, and the estimated local mucosal control rates in the re-LMP-1 positive and re-LMP-1 negative groups were 86.5%, 76.5%, 19.4%, and 96.7%, respectively. CONCLUSIONS: Expression of EBV LMP-1 in nasopharyngeal swab specimens from patients with irradiated/treated NPC can provide a highly sensitive and specific method of forecasting mucosal recurrence. This investigation confirmed the reliability and feasibility of nasopharyngeal swabs in screening for mucosal recurrences in patients with NPC.

Adult↗

PubMed1993

Analysis of Epstein-Barr virus infection in nasopharyngeal biopsies from a group at high risk of nasopharyngeal carcinoma.

Although Epstein-Barr virus (EBV) is consistently associated with the epithelial malignancy nasopharyngeal carcinoma (NPC), it is not clear to what extent the normal virus carrier state involves infection of nasopharyngeal epithelium. We attempted to examine this question by screening 26 nasopharyngeal punch biopsies from EBV-carrying Chinese Malaysians who had presented with clinical symptoms possibly indicative of NPC, but in whom histological analysis of an adjacent biopsy had revealed no evidence of tumour. Assays included (i) in situ hybridization with 35S-labelled riboprobes specific for EBERs (rather than with BamHI W DNA probes which can give false-positive results); (ii) cDNA amplification across defined splice junctions of the EBNA1 and BamHI A transcripts expressed in latently-infected NPC cells and of the BHRF1 lytic-cycle transcript; and (iii) immunostaining for the immediate early lytic-cycle protein BZLF1. Of the 26 biopsies examined, all 23 showing normal nasopharyngeal histology were consistently negative for both latent and lytic-cycle markers. The other 3 cases were all positive for EBNA1 and BamHI A transcripts; these RNAs were almost certainly of tumour rather than normal-cell origin since these particular biopsies were the only ones to reveal localized foci of EBER-positive NPC cells; such biopsies were again negative for lytic-cycle markers. We provisionally conclude that EBV infection of the normal nasopharynx is not a regular feature of the virus carrier state and that screening nasopharyngeal biopsies for viral RNA markers of the latent cycle could be useful in NPC diagnosis.

Base Sequence↗