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In situ detection of viral and cellular markers in nasopharyngeal carcinoma

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Title In situ detection of viral and cellular markers in nasopharyngeal carcinoma
Period 01 / 2006 - unknown
Status Completed
Research number OND1326598
Data Supplier Website V-ICI

Abstract

Current golden standard for diagnosis of EBV-linked nasopharyngeal carcinoma (NPC) requires an invasive biopsy and in situ detection of EBV-encoded small RNAs (EBER-RISH), which is a sensitive but cumbersome procedure, ill suited for developing countries. We defined specificity and developed new monoclonal antibodies to various EBV proteins expressed in NPC tumour cells 1,2 . This will permit in situ diagnosis by simple immunohistochemistry techniques 1 . EBNA1 (via OT1x MoAb) and LMP1 (via OT21C MoAb) can now reliably be detected, whereas LMP2, BARF0 and BARF1 expression in vivo is under study. EBNA1 is expressed in all tumour cells, but LMP1 shows more variable behaviour between NPC cases and is more abundant in childhood NPC, but did not seem to relate to clinical behaviour 1 . BARF1 is specifically expressed in NPC and EBV+ gastric cancer, but not in EBV+ lymphomas. BARF1is a novel viral oncogene with potential important functions in carcinogenesis and appears to be actively secreted from NPC cells 3 . Novel BARF1 antibodies have been made recently for in situ detection. Although little to no EBV lytic gene expression is detectable in NPC tumors, NPC patients have specific elevated IgA antibody responses in relating to disease progression 4 . Studies are in progress to locate EBV lytic gene expression and IgA-producijg plasma cells in NPC patients. We recently showed that apoptosis resistance within the tumour cells may be responsible for resistance to radiotherapy 5 . This may be counteracted by Adnenovirus-driven P53 genetherapy as suggested before 6 . The relation between LMP1 expression and cellular markers affecting local immune reactivity, hypoxia and tumor metastasis behaviour is currently under investigation.

Related organisations

Related people

Project leader Prof.dr. E. Bloemena
Project leader Prof.dr. J.M. Middeldorp
Project leader C. Murtono
Project leader Dr. J.J. Oudejans

Classification

D23120 Oncology
D23230 Neurology, otorhinolaryngology, opthalmology

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