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Epstein-Barr Viral RNA(EBERs) Expression in Conventional Malignant Lymphoma and Polymorphic Reticulosis of Upper Aerodigestive Tract.
Do Youn Park, Kang Suek Suh, Sun Kyung Lee
Korean J Pathol. 1996;30(10):893-902.
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AbstractAbstract PDF
The author examined the immunophenotype and expression of Epstem-Barr virus RNA (EBERs) used in the situ hybridization technique in 20 cases of conventional malignant lymphoma and 28 cases of polymorphic reticulosis and malignant lymphoma with features of polymorphic reticulosis occured in the upper aerodigestive tract including the upper digestive tract(palatine tonsil), and upper respiratory tract(nasal cavity, paranasal sinus, nasopharynx). The results obtained were summarized as followings; 1. The favorable site of malignant lymphoma that occured in the upper aerodigestive tract was in the palatine tonsil(11 out of 20 cases, 55%), those of polymorphic reticulosis and malignant lymphoma with features of polymorphic reticulosis were nasal cavity and nasopharynx(19 out of 28 cases, 78%). 2. The immunophentype of malignant lymphoma that occured in the upper aerodigestive tract was mostly B-cell phenotype (15 out of 20 cases, 75%), and that of polymorphic reticulosis and malignant lymphoma with features of polymorphic reticulosis was predominantly T-cell phenotype(22 out of 28 cases, 79%). 3. The EBERs positivity of malignant lymphoma that occured in the upper aerodigestive tract was 25%(5 out of 20 cases), but that of polymorphic reticulosis and malignant lymphoma with features of polymorphic reticulosis was 57%(16 out of 28 cases). 4. The positive cases for EBERs revealed angiocentricity with necrosis(16 out of 21 cases, 76%), predominantly T-cell phenotype(19 out of 21 cases, 90%), and favorably involved the nasal cavity and nasopharynx(16 out of 21 cases, 76%). Based on the above results, it was concluded that polymorphic reticulosis and malignant lymphoma with features of polymorphic reticulosis that occurred in the upper respiratory tract was an EBV-positive angiocentric T-cell lymphoma favorably involving the nasal cavity and nasopharynx.
Epstein-Barr Virus in Korean Malignant Lymphomas.
Young Hyeh Ko, Jung Dal Lee
Korean J Pathol. 1996;30(11):1011-1017.
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AbstractAbstract PDF
To determine the prevalence of Epstein-Barr virus infection in lymphoid neoplasms of various histology and location, the paraffin tissues of 74 non-Hodgkin's lymphomas and 13 Hodgkin's diseases were studied by EBER and BHLF RNA in situ hybridization as well as immunostaining using LMP-1, EBNA-2, and ZEBRA. As a control, non-neoplastic lymphoid tissues from the nasal cavity(10), lymph node(38) and Waldeyer's ring(12) were investigated. In non-neoplastic control, EBV genome was detected in none of 10 nasal mucosa, 6 of 38 lymph node, and 1 of 12 Waldeyer's ring. EBV-positive non-neoplastic lymphocytes expressed CD45RO in 2 cases and CD20 in 4 cases. Non-Hodgkin's lymphoma was positive for EBV in 37.8% of the cases in which T-cell lymphoma showed higher rate(56%) than B-cell lymphoma(15%), especially in nasal lymphoma(80%) and angiocentric lymphoma(63.6%). Hodgkin's disease was EBV positive in 38.4% of the cases. EBV genome in tumor tissue existed in latent form as well as in lytic form. LMP-1 was positive in 80% of Hodgkin's disease and 39% of non-Hodgkin's lymphoma in which EBV genome was detected. EBNA-2 was expressed in 3 cases of non-Hodgkin's lymphoma. On the basis of protein expression, most lymphomas belonged to type II latency. These results support that EBV is associated with pathogenesis of malignant lymphoma although its mechanism still awaits to be clarified.
Expression of Epstein-Barr Virus Gene Products, Bcl-2 and p53 Proteins in Nasopharyngeal Carcinomas.
Sun Hee Yoon, Kang Suek Suh, Chang Hun Lee
Korean J Pathol. 1997;31(8):723-734.
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AbstractAbstract PDF
The authors studied EBV genome expression in 40 conventionally processed samples of nasopharyngeal carcinomas (NPC), using in situ hybridization for EBERs and immunohistochemistry for LMP, Bcl-2 and p53 proteins. The NPCs consisted of 6 keratinizing squamous cell carcinomas (KSCs), 13 nonkeratinizing carcinomas (NKCs) and 21 undifferentiated carcinomas (UCs). The results were summarized as follows: 1) EBERs were expressed in 80.0% of all the NPCs (32/40). As for the subtypes, they were detected in 92.3% of NKCs (12/13), in 90.5% of the UCs (19/21), and in 16.7% of the KSCs (1/6). In positive cases, the nuclei of tumor cells displayed uniformly strong staining. 2) LMP was expressed in 10.0% of all the NPCs (4/40), all of which were UC. The LMP expression in the UCs was not correlated to the expression of EBERs, Bcl-2 and p53 proteins. 3) Bcl-2 protein was detected in 85.0% of all the NPCs (34/40). As for the subtypes, they were detected in 92.3% of the NKCs (12/13), in 90.5% of the UCs (19/21), and in 50.0% of the KSCs (3/6). 4) p53 protein was detected in 75.0% of all the NPCs (30/40). As for the subtypes, they were detected in 81.0% of the UCs (17/21), in 69.2% of the NKCs (9/13), and in 66.7% of the KSCs (4/6). 5) In the NPCs the expression of EBER showed a significantly positive correlation with that of p53 or Bcl-2 protein. The above results indicate that the association of EBV with NPC is chiefly with poorly differentiated and undifferentiated carcinomas. Additionally, carcinomas commonly display widespread, strong immunoreactivity of Bcl-2 and p53 proteins over tumor cells. In conclusion, these observations indicate that the EBV-association in NPC appears to contribute to the overexpression of tumor-related genes during carcinogenesis.
Detection and Subtyping of Epstein-Barr Virus in Gastrointestinal Adenocarcinomas and Malignant Lymphomas.
Young Sik Kim, Seol Hee Park, In sun Kim
Korean J Pathol. 1997;31(9):847-861.
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AbstractAbstract PDF
Epstein-Barr virus (EBV) has been linked to a spectrum of neoplastic conditions, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, lymphoepithelioma-like carcinomas and malignant lymphomas in immunocompromised state. To determine the prevalence and the subtype of EBV in gatrointestinal malignancies, fifty cases of adenocarcinomas and seventeen cases of malignant lymphomas were analyzed by EBERs in situ hybridization and polymerase chain reaction using primers for EBNA-1, EBNA-2A and EBNA-2B, on the paraffin sections. In addition, immunohistochemical stain for p53 protein was performed to investigate the potential role of EBV infection on tumor suppressor gene, p53, during tumorigenesis. EBER was detected in 6 of 26 gastric adenocarcinomas, 2 of 24 colon adenocarcinomas, and 8 of 17 malignant lymphomas. EBER was more prevalent in malignant lymphoma arising in the intestine (6/6) than in the stomach (2/11), and was detected in both B and T cell phenotypes. EBNA-1 was positive in 11 of 16 EBER positive cases and the subtyping was possible in 8; both type 1 and 2 were detected in gastric cancers, whereas only type 2 was found in intestinal neoplasms. In adenocarcinomas the high rate of p53 protein overexpression was found in both EBER positive (8/8) and negative cases (32/42), whereas the positive rate was higher in EBER positive cases (7/8) than in EBER negative cases (4/9) of malignant lymphomas. From the results, it can be concluded that EBV infection and the p53 tumor suppressor gene are independently associated in a significant portion of the gastrointestinal malignancies, but the mechanism of action remains to be elucidated.
Application of Epstein-Barr Virus Cell Lines (CCL85 EB-3) in Performing the EBER mRNA In Situ Hybridization as a Positive Control.
Sung Sook Kim, Woon Sup Han, Joo Young Suh, Joo Ryung Huh
Korean J Cytopathol. 1996;7(1):38-43.
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AbstractAbstract PDF
Epstein-Barr virus(EBV) is associated with a wide spectrum of benign and malignant disorders including leukoplakia, Hodgkin's lymphoma, central nervous system lymphoma, peripheral T cell lymphoma and nasopharyngeal undifferentiated carcinoma. There are several distinctive aspects of biology of the virus that are important in investigation of virus in clinical specimens. The abundant expression of the EBER mRNA transcripts makes possible the sensitive detection of latent expression in EBV-associated tumors. Although there has been a dramatic increased interest in the direct characterization of EBV in clinical specimens, there have been few studies about the effective and reliable positive controls in performing in situ hybridization technique for EBV, especially on paraffin-embedded tissue. We applied Burkitts lymphoma cell line as positive control in EBV in hydridization using Oncor Kit. The cell block of Burkitt lymphoma cell line(CCL85 EB-3) showed strong and specific positivity for EBER in situ in nuclei of EBV infected cells.

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