Molecular pathology parameters in human nasopharyngeal carcinoma

Authors

  • Wei Shi M.D.,

    1. Department of Research, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
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  • Istvan Pataki M.D.,

    1. The Cancer Institute of New Jersey–Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ
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  • Christine MacMillan M.D.,

    1. Department of Pathology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Laboratory Medicine, University of Toronto, Toronto, Canada
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  • M. Pintilie M.Sc.,

    1. Department of Biostatistics, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
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  • David Payne M.D.,

    1. Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Radiation Oncology, University of Toronto, Toronto, Canada
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  • Brian O'Sullivan M.B.,

    1. Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Radiation Oncology, University of Toronto, Toronto, Canada
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  • Bernard J. Cummings M.B. Ch.B.,

    1. Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Radiation Oncology, University of Toronto, Toronto, Canada
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  • Padraig Warde M.B.,

    1. Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Radiation Oncology, University of Toronto, Toronto, Canada
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  • Fei-Fei Liu M.D.

    Corresponding author
    1. Department of Research, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
    3. Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada
    4. Department of Radiation Oncology, University of Toronto, Toronto, Canada
    • Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada
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    • Fax: (416) 946-4586


Abstract

BACKGROUND

To derive a better understanding of the biologic behavior of nasopharyngeal carcinoma (NPC), the authors evaluated a number of molecular variables to address the hypothesis that p53 dysfunction in NPC is associated with Epstein-Barr virus (EBV), increased tumor angiogenesis, lower likelihood of apoptosis, and poorer clinical outcome.

MATERIALS

The biopsy samples from 87 NPC patients were obtained and sections were made to detect EBV, using in-situ hybridization; the authors used immunohistochemistry to assess p53, p21WAF1/CIP1 expression, and microvessel density count (MVD). In situ end labelling was used to evaluate apoptosis and necrosis. Analyses were conducted on the association between each of these variables as well as clinical outcome, including survival and local control.

RESULTS

There was a highly significant association between EBV-encoded RNA (EBER) positivity with p53 over-expression in that only 1 out of 32 p53 over-expressing tumors was EBER negative, as opposed to 19 out of 48 p53 negative tumors being EBER negative (P = 0.001). In addition, EBER positivity was highly associated with World Health Organization (WHO) type 3 NPC, Asian/Chinese ethnicity, a lower apoptotic index, and p21 over-expression. p53 over-expression was associated with a higher MVD count. Controlling for age and nodal status, EBER positivity was associated with both improved overall survival (P = 0.02), and disease-free survival (P = 0.04). In contrast, the presence of tumor necrosis was associated with an inferior local control (P = 0.03).

CONCLUSION

p53 protein was over-expressed in approximately one third of NPC samples in the current study, and this correlated significantly with the presence of EBER. Epstein-Barr virus status was also associated with WHO type 3 NPC, Asian/Chinese ethnicity, and induction of p21. The presence of EBV appeared to predict for improved survival, the mechanism of which remains to be elucidated in this biologically complex disease. Cancer 2002;94:1997–2006. © 2002 American Cancer Society.

DOI 10.1002/cncr.10440

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