Detection of epstein‐barr virus DNA in formalin‐fixed paraffin‐embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization

Akao, Ichiro; Sato, Yuichi; Mukai, Kiyoshi; Uhara, Hisashi; Furuya, Shuichiroh; Hoshikawa, Tomohide; Shimosato, Yukío; Takeyama, Isamu

doi:10.1288/00005537-199103000-00010

Cited by 53 publications

(18 citation statements)

References 20 publications

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“…The presence of the EBV genome in the differentiated forms of NPC was recently reported. 17,18) We confirmed this in the present study; i.e., the EBV genome was also found in the tumor cells of moderately and well-differentiated SCC, though much less frequently than in the poorly differentiated form. The stable maintenance of EBV in epithelial cells of undifferentiated condition was reported by Knox et al 19) This might be one of the reasons for the high EBV-association in NPC.…”

Section: Discussionsupporting

confidence: 89%

Site‐specific Localization of Epstein‐Barr Virus in Pharyngeal Carcinomas

Kojya¹,

Itokazu²,

Noda³

et al. 1998

Japanese Journal of Cancer Research

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In this study, the correlations of factors with Epstein-Barr virus (EBV)-association were investigated in 50 patients with nasopharyngeal carcinoma (NPC), 61 with oropharyngeal carcinoma (OPC), and 55 with hypopharyngeal carcinoma (HPC) in Okinawa and Osaka prefectures in Japan. The incidence of pharyngeal carcinoma in Okinawa was previously found to be higher than that in Osaka; the incidence of OPC was approximately 6 times higher and that of HPC was two times higher. The EBV genome was detected in the tumor cells of the present patients; 83% of the Okinawa and 92% of the Osaka NPC patients. The EBV genome was not detected in OPC or HPC. A univariate analysis showed that sex, the location of the tumor, histology, and the degree of lymphocytic infiltration correlated with the EBV-positive rate. A multivariate analysis revealed that only the location of the tumor was independently correlated with the EBV-positive rate. Histology and tumor size were factors affecting the prognosis of the patients with NPC. The NPC of poorly differentiated type frequently showed the EBV genome, and NPC with lymphocytic infiltration showed a more favorable prognosis compared to the other NPC types. These findings suggest that latent genes of EBV expressed in cancer cells might trigger a cytotoxic T cell reaction against the cancer. Key words: Epstein-Barr virus -Pharyngeal carcinoma -EpidemiologyEpstein-Barr virus (EBV), a herpesvirus which can infect lymphocytes, was originally discovered in cultured lymphoblasts from the African type of Burkitt's lymphoma in 1964.1) An oncogenic role of EBV in the development of B cell lymphoma and nasopharyngeal carcinoma (NPC) was subsequently suggested.2) Recent studies have shown the presence of EBV sequences in carcinoma cells of thymic, 3) gastric, 4) salivary gland, 5,6) and lung cancers. 7)The pharyngeal space is divided into three parts; the nasopharynx, oropharynx, and hypopharynx. The nasopharynx is covered with pseudostratified respiratory epithelium, and the oropharynx and hypopharynx are covered with stratified squamous epithelium. The naso-and oropharynxes have well-developed lymphoid tissue, i.e., Waldeyer's ring, whereas the hypopharynx is devoid of lymphoid tissue. The association of EBV with NPC is well-known, and it has been reported that EBV-associated NPC usually have poorly differentiated morphology accompanied by severe lymphoid cell infiltration, forming a lymphoepitheliomatous lesion. It is not yet evident whether oropharyngeal and hypopharyngeal carcinomas (OPC and HPC), especially those of the poorly differentiated type, are EBV-associated.We recently reported a much higher frequency of sinonasal lymphoma in Okinawa prefecture compared to Osaka in Japan, and we showed that the majority of these lymphomas were associated with EBV.8) The incidence of pharyngeal carcinoma in Okinawa was also found to be higher than that in Osaka; the incidence of OPC is approximately 6 times higher and that of HPC is two times higher in Okinawa. 9) In the present study, we investigated wh...

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Section: Discussionsupporting

confidence: 89%

Site‐specific Localization of Epstein‐Barr Virus in Pharyngeal Carcinomas

Kojya¹,

Itokazu²,

Noda³

et al. 1998

Japanese Journal of Cancer Research

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“…However, the evidence regarding the possibility of an EBV association with keratinizing squamous cell NPC has been conflicting. The studies from Raab-Traub et al [1987] and other laboratories [Pathmanathan et al, 1995;Chen et al, 1993;Dickens et al, 1992;Akao et al, 1991] indicated that keratinizing NPC from Asian patients are associated regularly with EBV. But Niedobitek et al [1991] failed to detect the virus in such tumours from Caucasian patients, and similar observation were also obtained from some other groups [Hording et al, 1993;Nicholls et al, 1997;Klein et al, 1974].…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma

et al. 1998

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Three stages of maturation can be seen in keratinizing nasopharyngeal carcinomas. These stages are similar morphologically to basal cells, intermediate and superficial squamous cells seen in normal squamous epithelium. Taking advantage of such a diverse tumour cell population, 10 keratinizing nasopharyngeal carcinoma (NPC) were examined by in situ hybridization for the presence of latent Epstein-Barr Virus (EBV) using EBV encoded RNAs (EBERs) and by immunohistology for the presence of EBV early antigen-diffuse (EA-D) and the 350/220 kd membrane glycoprotein of the EBV. The basal cell-like tumour cells are mainly infected latently with the virus; viral replication was found in isolated intermediate squamous cells, whilst superficial squamous cells are largely depleted of all the viral markers. We used a control series of nonkeratinizing nasopharyngeal carcinomas composed of undifferentiated and poorly differentiated tumour cells and EBV latency was present in these tumours. Viral replication was detected by RT-PCR, in the undifferentiated tumours but viral replication was not seen by immunohistology. The possible relationship between EBV life cycle in these tumours and tumour cell differentiation is discussed in the light of these findings.

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“…Virus-related pathologies can occur, however, and are of particular concern in immunocompromised individuals (4,5,48). EBV is associated with the development of several malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, and various lymphoproliferative disorders arising in immunocompromised patients (2,3,4,15,37,74).…”

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confidence: 99%