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.

Detection of Stage I nasopharyngeal carcinoma by serologic screening and clinical examination.

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.

[Study of sequence variations of Epstein-Barr virus LMP1 gene in nasopharyngeal carcinoma].

OBJECTIVE: To detect the sequence variations frequently found within the N- and C-terminal regions of Epstein-Barr virus (EBV) LMP1 gene in nasopharyngeal carcinoma (NPC) and to study the underlying mechanisms. METHODS: Fresh tumor tissues were sampled from 63 patients with untreated NPC encountered in Affiliated Tumor Hospital of Sun Yat-sen University, Guangzhou. The N-terminal region of EBV LMP1 gene was amplified with nested polymerase chain reaction (PCR), followed by XhoI enzyme digestion. Nested PCR was also employed to detect the 30 base pairs deletion within the C-terminal region. Four-colored fluorescence terminator sequencing method was applied for bi-directional solid-phase sequencing of the 8 representative PCR products in 4 cases of NPC. The DNA sequence within the N- and C-terminal regions of LMP1 gene was then analyzed. RESULTS: There were 4 patterns of sequence variations, namely, wt-XhoI/wt-LMP1 (4 cases, 6.3%), wt-XhoI and XhoI-loss/del-LMP1 (4 cases, 6.3%), wt-XhoI/del-LMP1 (5 cases, 7.9%) and XhoI-loss/del-LMP1 (50 cases, 79.5%), detected in the 63 studied cases. Sequence analysis showed that the EBV LMP1 gene had underwent non-synonymous and synonymous substitutions, as compared with the prototype of B95-8 cells. The ratio of non-synonymous to synonymous substitutions was 2.25. CONCLUSIONS: XhoI-loss/del-LMP1 is the predominant sequence variation pattern of EBV LMP1 gene in NPC from Guangzhou. The XhoI-loss variation seems to develop on top of del-LMP1. When compared with the EBV LMP1 gene in peripheral blood B-lymphocytes of virus carriers and in preinvasive epithelial lesions (reported previously), it is likely that the sequence variation patterns of LMP1 gene may represent 4 different phases of intrahost evolution of EBV during nasopharyngeal carcinogenesis.

Detection of Epstein-Barr virus DNA in plasma/serum: a useful serological indicator for diagnosis of nasopharyngeal carcinoma.

OBJECTIVE: To compare the detection rates of Epstein-Barr virus (EBV) DNA in the serum/plasma between apparently healthy adults (AHAs) and nasopharyngeal carcinoma (NPC) patients in attempt to evaluate the efficiency of EBV DNA assay for serodiagnosis of NPC. METHODS: The plasma and serum were obtained from 58 AHAs and 66 untreated NPC patients. EBV DNA W-fragment was detected using nested ploymerase chain reaction (PCR). Immunoenzymatic assay for titration of IgA-VCA was also adopted. RESULTS: EBV DNA detection rate (84.85%) in the plasma/serum of 66 NPC patients was significantly higher than that (10.34%) in 58 AHAs. The sensitivity of plasma/serum EBV DNA assay (0.8485) was higher than that (0.8030) of titrating IgA-VCA (positive criterion >/= 1:40) though the specificities of these two tests were the same (0.8966). The correct rate, predictive value of a positive test, and Odds ratio of dual positivity (0.8387, 0.9792 and 141.0, respectively) were higher than those of single positivity either to plasma/serum EBV assay (0.5242, 0.7333 and 1.1423, respectively) or to IgA-VCA >/= 1:40 test (0.4839, 0.5385 and 1.0480, respectively). CONCLUSION: The EBV DNA detection in the plasma/serum using nested PCR may be a useful indicator for serodiagnosis of NPC.

Primary nasopharyngeal non-Hodgkin lymphoma and its relationship with Epstein-Barr virus infection.

OBJECTIVES: To investigate the immunophenotypes of primary nasopharyngeal non-Hodgkin lymphoma (NPL) and their relationship to Epstein-Barr virus (EBV) infection. METHODS: The clinical data and biopsies of 73 patients with NPL were collected in Guangzhou. In situ hybridization was performed to detect the EBV-encoded small non-polyadenylated nuclear RNAs (EBERs) on biopsy slides. Immunohistochemistry was used to classify the immunophenotypes of NPL and detect EBV antigen expression. RESULTS: Forty-four (60.27%) of the 73 NPLs were of B cell lineage (CD79alpha(+)/CD3(-)/CD56(-)) while the 29 others (39.73%) were of non-B cell lineage. Seventy-three NPLs could be classified into 3 major immunophenotypes: B cell (CD79alpha(+)/CD3(-)/CD56(-), 44 cases), peripheral T cell (CD79alpha(-)/CD3(+)/CD56(-), 22) and NK/T cell (CD79alpha(-)/CD3(+)/CD56(+), 7). The percentages of EBV infection differed among the 3 major immunophenotypes (B cell: 11.36%, 5/44; peripheral T cell: 81.82%, 18/22; NK/T cell: 100%, 7/7). Both CD56(-) positive and CD56(-) negative immunophenotypes could further be divided into 4 subtypes: CD8(-)/CD4(-), CD8(+)/CD4(-), CD8(-)/CD4(+) and CD8(+)/CD4(+). All the CD8(-)/CD4(-) NPLs with CD56(-) positivity (7) or CD56(-) negativity (2) were infected with EBV. The neoplastic cells of a nasopharyngeal Burkitt's lymphoma expressed EBV nuclear antigen 1 (EBNA1) and EBV RNA (EBERs) only. In the other 29 EBV-infected NPLs, most of the lymphoma cells harboring EBV also expressed EBNA1 and EBERs; 21 of the 29 NPLs had a considerable number of neoplastic cells expressing latent membrane protein 1 (LMP1) (21/29, 72.41%) and 23 of 29 NPLs expressed latent membrane protein 2A (LMP2A) (23/29, 79.31%). A few lymphoma cells in 17 (17/29, 58.62%), 23 (23/29, 79.31%) and 22 NPLs (22/29, 75.86%) expressed Zta (Bam HI Z transactivator), viral capsid antigen (VCA) and membrane antigen (MA), respectively. CONCLUSIONS: The prevalence ratio of the 3 immunophenotypes, namely, B cell, peripheral T cell and NK/T cell lymphoma, is about 6:3:1. However, the EBV infection ratio is reversed, 1:8:10. All the NK/T cell (CD56(+)) and peripheral immature T cell (CD3(+)/CD8(-)/CD4(-)) NPLs were EBV-infected. Except for one Burkitt's lymphoma, the EBV harbored in both B cell and non-B cell NPLs was mainly latent infection, type II, expressing EBNA1, LMP1 and LMP2A. However, the EBV found in a few lymphoma cells could become replicative, expressing lytic proteins.

Enhancing the efficiency of Epstein-Barr viral serologic test in the diagnosis of nasopharyngeal carcinoma.

OBJECTIVE: To investigate the efficiency of concurrent application of VCA-IgA, EA-IgA and EA-IgG serological tests in diagnosing nasopharyngeal carcinoma (NPC). METHODS: The sera of 266 untreated NPC patients and 347 healthy adults were collected. In addition to the conventional immunoenzymatic method of VCA-IgA test, enzyme-linked immunosorbent assay (ELISA) was adopted as an alternative to test the antibody level of EA-IgG and EA-IgA. A new statistical formula was used to evaluate the odds ratio of different combinations of these three tests. RESULTS: The sensitivity and specificity of VCA-IgA, EA-IgG and EA-IgA concurrently were as high as 95.11% and 97.41%, respectively, which were higher than those of single test (90.60% and 94.52% for VCA-IgA, 93.98% and 93.66% for EA-IgG, 89.84% and 88.18% for EA-IgA). Furthermore, the odds ratio of 3-test positivity (1 912.5) was higher than those of 2-test positivity (27.903 2 for VCA-IgA and EA-IgG, 11.169 0 for EA-IgG and EA-IgA, 8.032 8 for VCA-IgA and EA-IgA), which were even higher than those of 1-test positivity (0.121 4 for VCA-IgA, 0.170 5 for EA-IgG and 0.048 8 for EA-IgA). CONCLUSION: ELISA is more accurate in reflecting the antibody level of EA-IgG and EA-IgA than the conventional immunoenzymatic method. The concurrent application of VCA-IgA, EA-IgG and EA-IgA test can markedly improve the sensitivity, specificity and odds ratio as well, thus resulting in enhancing the efficiency of diagnosing nasopharyngeal carcinoma serologically.

[Value of EBNA1-IgA and EA-IgG in serological diagnosis of nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the value of EBNA1-IgA and EA-IgG in serological diagnosis of nasopharyngeal carcinoma (NPC). METHODS: The serum EBNA1-IgA and EA-IgG of 56 patients with NPC and 58 healthy adults were detected by ELISA. The sensitivity, specificity, positive predictive value, accuracy rate and odds ratio of the two tests used singly or in combination were compared with each other. RESULTS: The sensitivity of EBNA1-IgA (91.07%) was higher than that of EA-IgG (87.50%), while the specificity of EA-IgG (87.93%) was higher than that of EBNA1-IgA (84.48%). The combination of EBNA1-IgA and EA-IgG could enhance the specificity (94.83%), positive predictive value (0.9375), likelihood ratio (15.5435) and odds ratio (75.0000) for serological diagnosis of NPC. Forty-five patients showed both positive EBNA1-IgA and positive EA-IgG. A positive EA-IgG was detected in 4 out of 5 patients with negative EBNA1-IgA and a positive EBNA1-IgA was founded in 6 out of 7 patients with negative EA-IgG. CONCLUSION: Although relatively high sensitivity and specificity could be obtained by either EBNA1-IgA or EA-IgG test alone, the combination of these two tests with a complementary effect is able to enhance the reliability of serological diagnosis of NPC as most patients have positive ENBA1-IgA and EA-IgG concurrently.

[Assessment of nasopharyngeal carcinoma risk by EB virus antibody profile].

OBJECTIVE: To evaluate the risk of nasopharyngeal carcinoma (NPC) through EB virus antibody profile by enzyme linked immunosorbent assay (ELISA). METHODS: EBNA 1/IgA, EBNA 1/IgG and zta/IgG by ELISA and VCA/IgA by immmunoenzymatic method were detected in 121 NPC patients and 332 healthy subjects (HS) in the Pearl river estuary. RESULTS: The sensitivity rates were 85%, 83% and 79% for EBNA 1/IgA, EBNA 1/IgG and zta/IgG, all three of which if combined was the highest 92%. The specificity rates were 86%, 86% and 80% for EBNA 1/IgA, EBNA 1/IgG and zta/IgG, all three of which if combined was also the highest 93%. According to the level of odds ratio, nasopharyngeal carcinoma risk could be divided into 3 groups: low, moderate and high-risk groups. 93% of HS had low risk of NPC with the odds ratio 0.0 to 0.3. 0.4% of HS had high risk of NPC with the odds ratio of 137.9%. CONCLUSION: ELISA is more objective than the traditional immunoenzymatic method in the detection and diagnosis of NPC. The combination of EBNA 1/IgA, EBNA 1/IgG and zta/IgG is able to evaluate the risk of NPC.

[Comparison of the Epstein-Barr virus infection and 30 bp-deleted LMP1 gene among 4 histologic types of nasopharyngeal carcinoma].

OBJECTIVE: To compare the Epstein-Barr virus (EBV) infection rates and the frequencies of wt-LMP1 and del-LMP1 EBV variants detected singly or dually among the four types of nasopharyngeal carcinoma (NPC) and to illustrate the possible role of del-LMP1 gene in nasopharyngeal carcinogenesis. METHODS: EBER in situ hybridization was performed in 117 NPCs, including 48 non-keratinizing carcinomas (NKCs), 25 keratinizing squamous cell carcinomas (KSCCs), 5 adenosquamous carcinomas (ASCs), 6 mucoepidermoid carcinomas (MECs) and 33 adenocarcinomas (ACs). Nested PCR for demonstration of EBV LMP1 gene was performed on the tissue samples collected from 99 EBER-positive carcinoma cases and the peripheral blood mononuclear cells (PBMCs) of 53 healthy adults (HAs). RESULTS: As indicated by EBER in-situ hybridization, the EBV infection rates in both of 48 NKCs and 25 KSCCs were 100%; and the infection rates of 11 ASCs/MECs and 33 ACs were 9/11 and 51.5% (17/33), respectively. Worthy to note was that most of the NKC cells were EBER-positive while only a small number of EBER-positive neoplastic cells could be found in 17 ACs. The percentage of del-LMP1 EBV variant detected singly in NKCs (85.4%, 41/48) was not only significantly higher than that in PBMCs of 46 HAs (8.7%, 4/46) but also significantly higher than those detected in KSCCs (16.0%, 4/25). The dual infection rate of wt-LMP1 and del-LMP1 variants detected in KSCCs (56.0%, 14/25) was significantly higher than that of NKCs (12.5%, 6/48). The majority of the EBV detected in AC tissues (12/17) and HAs' PBMCs (34/46, 73.7%) were of dual wt-LMP1 and del-LMP1 variants. CONCLUSIONS: The EBV infection rates are significantly different among 3 major histological categories, namely, NKC/KSCC, ASC/MEC and AC. Though NKCs and KSCCs are always consistently associated with EBV, the single del-LMP1 EBV variant detected in NKCs is predominant over that in KSCCs and most of the KSCCs contain dual wt-LMP1 and del-LMP1 EBV variants. The EBV of the del-LMP1 variant might play a crucial role in carcinogenesis of NKC.

[Primary adenoid cystic carcinoma of the nasopharynx and its relation to Epstein-Barr virus infection].

OBJECTIVE: To investigate the clinicopathologic characteristics of primary nasopharyngeal adenoid cystic carcinoma (NPACC) and its relation to Epstein-Barr virus (EBV) infection in Guangzhou where is a high-incidence area of EBV-associated nasopharyngeal carcinoma (NPC). METHODS: 17 cases of NPACC with clinical record and biopsy samples were collected in Guangzhou and their clinical manifestations were reviewed. Besides HE, Alcian blue and PAS, LSAB immunohistochemistry was performed for detecting the expression of a variety of epithelial markers, CD21 and EBV encoded LMP1. EBV encoded early RNAs (EBER) was detected by using in-situ hybridization. Nested PCR was applied for studying the presence of EBV W-fragment in tissues. RESULTS: The ratio of male to female was 7:10. The patients' age ranged from 30 to 63 years, and the median age was 46 years. 14 out of 17 tumors showed markedly local aggressive growth, presenting as T3 or T4. However, only 1 patient had metastasis of an ipsilateral cervical lymph node. The majority of neoplastic cells were basal-cell like in shape and with scanty cytoplasm and a deeply stained nucleus. Intercellular hyaline or mucinous substance was always present in between the carcinoma cells. Cribriform structure formed by the neoplastic cells could be found in 16 out of these 17 biopsies. The NPACC always express the wide-spectrum cytokeratin and the epithelium membrane antigen. Only a few or a small number of carcinoma cells showed nuclear EBER-signals in 9 cases (9/17). Concurrently, these 9 NPACCs showed a 192 bp W-fragment positive band on electrophoresis gel by nested PCR. LMP1 expression had been found in 5 out of the 9 NPACCs (55.6%) accompanying with EBER-positive carcinoma cells. The EBER-positive infiltrating lymphocytes could also be found in the stroma of 3 out of the 9 EBER-stained NPACC slides. All the tumor cells, including the EBER-positive cell of the 17 NPACCs showed no CD21 expression. CONCLUSIONS: The female is predominant over the male in development of NPACC, which often accompanied with a markedly invasive capacity at the nasopharynx and its neighboring sites. Only a small number of tumor cells, nearly a half of the studied cases were infected with EBV. Therefore, it's postulated that there seems no close relation present between NPACC and EBV infection.

[Analysis of Epstein-Barr virus with BamHI "f" variant and XhoI-loss of LMP1 gene in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the genomic variation of Epstein-Barr virus (EBV) and its significance in nasopharyngeal carcinogenesis. METHODS: Forty nasopharyngeal carcinoma (NPC) biopsy tissues were used for detection of EBV BamHI f variant and LMP1 XhoI-loss by polymerase chain reaction (PCR), nested PCR, and RFLP (restriction fragment length polymorphism). Forty-eight samples of peripheral blood mononuclear cells (PBMC) taken from apparently healthy adult individuals were used for detection of LMP1 XhoI-loss. Three samples of amplified LMP1 exon 1 DNA from B95-8 cell line and 2 NPC tissues (one having XhoI-loss and the other having Wt-XhoI/XhoI-loss) were sequenced. RESULTS: Thirty out of the 40 NPC cases (30/40, 75%) harbored EBV BamHI f variant and the remaining 10 (10/40, 25%) harbored BamHI F prototype. Thirty out of the 39 NPCs (30/39, 76.9%) showed single EBV LMP1 XhoI-loss, 7 (7/39, 18.0%) showed single LMP1 Wt-XhoI (presence of a XhoI site in exon 1 of LMP1 gene, as in B95-8 cell line), and 2 (2/39, 5.1%) showed both LMP1 Wt-XhoI and XhoI-loss. Thirty-eight of the 39 NPCs (97.4%) showed EBV LMP1 XhoI-loss or/and BamHI F variant. In the NPC tissue (1 case only) showing the prototype of Wt-XhoI/BamHI "f", there were several base substitutions, including 5 missense mutations and 2 silent mutations present in LMP1 exon 3, on DNA sequencing. On the other hand, 10 out of the 48 samples of PBMC taken from apparently healthy individuals could be amplified successfully by nested PCR for detection of LMP1 XhoI site. All of these 10 samples carried the prototype of EBV LMP1 Wt-XhoI. CONCLUSIONS: The majority of EBV present in neoplastic cells of NPC is of BamHI "f" variant and/or possesses LMP1 XhoI-loss, as compared with that in healthy individuals. This genomic variation of EBV may bear some roles in the development and progression of NPC.

Nasopharyngeal extranodal NK/T-cell lymphoma, nasal type: retrospective study of 18 consecutive cases in Guangzhou, China.

OBJECTIVE: The aim of this study was to investigate the frequency and clinicopathologic features of nasopharyngeal extranodal NK/T-cell lymphoma, nasal type (NKTCL), as well as DNA sequence variation of Epstein-Barr virus (EBV) in neoplastic cells harboring in NKTCLs from Guangzhou district. MATERIALS AND METHODS: The clinical data of 18 unselected consecutive nasopharyngeal NKTCLs in one institution were reviewed retrospectively. Immunohistochemical staining and EBV-encoded RNAs (EBERs) in situ hybridization were applied. DNA extraction, polymerase chain reaction (PCR), nested PCR, and sequencing for analyzing the C-terminal and N-terminal regions of LMP1 gene as well as BamHI F fragment of EBV were applied in 16 available samples. RESULTS: NKTCLs accounted for 69.2% (18/26) of nasopharyngeal T- and NK-cell lineage non-Hodgkin lymphomas. In all, 10 out of 18 patients (55.56%) had cervical lymph node(s) involvement. The serum anti-EBV antibody level was elevated (VCA-IgA titer ≥1:40) in 6 of 12 available patients. Two major immunophenotypic subtypes, namely, TIA-1+/EBERs+/CD56+ (10 cases) and TIA-1+/EBERs+/CD56- (8 cases) could be recognized. Genotyping analysis revealed that 10 out of 13 cases (76.9%) of NKTCL were harbored with del-LMP1 [del-LMP1 (Gly335) variant 7 cases, del-LMP1 (Asp335) variant 3 cases]. XhoI-loss was shown in 8/11 cases (72.73%). BamHI "f" variant of Bam F fragment was shown only in 4/14 cases (28.57%).The most common combination was del-LMP1 (Gly335)/ XhoI-loss/F (6/9, 66.7%). CONCLUSIONS: The majority of nasopharyngeal T- and NK-cell lymphomas are NKTCL in Guangzhou district. The patients often have involvement of cervical lymph node(s) and an elevated level of serum anti-EBV antibodies. The CD56 expression rate seems lower than that found in sinonasal NKTCL. The most common EBV variant harboring in nasopharyngeal NKTCL seems somewhat different from that harboring in nasopharyngeal carcinoma in Guangzhou.

Heat shock factor 1 upregulates transcription of Epstein-Barr Virus nuclear antigen 1 by binding to a heat shock element within the BamHI-Q promoter.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for maintenance of the episome and establishment of latency. In this study, we observed that heat treatment effectively induced EBNA1 transcription in EBV-transformed B95-8 and human LCL cell lines. Although Cp is considered as the sole promoter used for the expression of EBNA1 transcripts in the lymphoblastoid cell lines, the RT-PCR results showed that the EBNA1 transcripts induced by heat treatment arise from Qp-initiated transcripts. Using bioinformatics, a high affinity and functional heat shock factor 1 (HSF1)-binding element within the -17/+4 oligonucleotide of the Qp was found, and was determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Moreover, heat shock and exogenous HSF1 expression induced Qp activity in reporter assays. Further, RNA interference-mediated HSF1 gene silencing attenuated heat-induced EBNA1 expression in B95-8 cells. These results provide evidence that EBNA1 is a new target for the transcription factor HSF1.

[Six anti-Epstein-Barr virus antibodies in healthy adults in a high risk area of nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: Nasopharyngeal carcinoma (NPC), with a remarkable geographic distribution, is consistently associated with Epstein-Barr virus (EBV) infection, and almost all NPC patients have sustained high levels of serum antibodies against EBV. This study was to compare the levels of six anti-EBV antibodies in healthy natives of Zhongshan (a high-incidence area of NPC) with those in provisional migrants from foreign provinces (low-incidence areas of NPC), and to illustrate the relationship between EBV infection and the geographic distribution of NPC. METHODS: The serum levels of EBNA1-IgA, EBNA1-IgG, VCA-p18-IgA, VCA-p18-IgG, Zta-IgA and Zta-IgG in 303 healthy Zhongshan natives and 92 provisional migrants were tested using ELISA, and presented by values of adjusted relative absorbance (ArA). The serum levels and positive rates of the six antibodies were compared between the two groups. RESULTS: The mean ArA values of both Zta-IgA and VCA-p18-IgA were significantly higher in Zhongshan natives than in provisional migrants (0.84+/-0.03 vs. 0.42+/-0.04, P <0.05; 0.96+/-0.05 vs. 0.40+/-0.05, P<0.05). In addition, the positive rates of Zta-IgA and VCA-p18-IgA in subjects aged of 30-49, or of 50 and above were significantly higher in Zhongshan natives than in provisional migrants (29.27% vs. 3.03% and 48.28% vs. 6.67% for Zta-IgA, P<0.05; 28.46% vs. 9.09% and 43.10% vs. 13.33% for VCA-p18-igA, P<0.05). CONCLUSION: Zhongshan natives are likely to have an elevation of serum IgA antibodies against EBV lytic antigens (Zta and VCA-p18), which represents reactivation of EBV latency infection and implies that Zhongshan natives may have higher risk to develop NPC than provisional migrants.

Clinicopathologic features and Epstein-Barr virus infection status of Burkitt's lymphoma in Guangzhou district.

BACKGROUND AND OBJECTIVE: Sporadic Burkitt's lymphoma (sBL) is uncommon and its relation to Epstein-Barr virus (EBV) is unknown in China. This study was to investigate the clinical presentation, morphologic features, immunophenotype and EBV infection status of sBL in Guangzhou district, a prevalent area of EBV infection. METHODS: The clinical data of 21 sBL patients were reviewed. A panel of immunohistochemical staining was performed and EBV-encoded small RNAs (EBERs) in situ hybridization was applied to identify EBV infection. RESULTS: From January 2000 to October 2007, 21 cases(0.87%) of sBL were confirmed among 2416 cases of non-Hodgkin's lymphoma(NHL) in Sun Yat-sen University Cancer Center. Male to female ratio was 4.25 (17/4). The median age was 23 years. Of the 21 patients, 19 (90.48%) had lymph node(s) involvement; 16 (76.19%) had multiple sites involvement; 12 (57.14%) were at advanced stages (III/IV). The 2-year survival rate of 15 patients who received chemotherapy or resection plus chemotherapy was 56.00%. Twenty cases showed the prototypic morphology of sBL, and one was the variant of sBL with plasmacytoid differentiation. The main immunophenotype of these 21 sBLs was sIgM+/CD20+/CD10+/Bcl-6+/Bcl-2-[or Bcl-6+(>95%)/Bcl-2+(<10%)]/TdT-/Ki-67+ 100%. Of 20 detectable cases, 11 showed CD5 expression in a few (3%-20%) tumor cells. P53 was overexpressed in ten cases (47.62%). Six cases (28.57%) had EBV infection, with EBNA1 and EBERs expression, but not LMP1. There were no significant differences in morphology and immunophenotype between EBV-positive and EBV-negative cases. CONCLUSIONS: sBL is uncommon in Guangzhou district, mainly seen in boys and young men. Most patients had lymph node(s) involvement, showing similar morphology and immunophenotype as that of endemic BL. Type I EBV latent infection is associated with 28.57% of cases.