Molecular pathology parameters in human nasopharyngeal carcinoma.
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.


METHODS
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, p21(WAF1/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).


CONCLUSIONS
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.
Shi
Wei
W
Department of Research, Princess Margaret Hospital/Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada.
Pataki
Istvan
I
MacMillan
Christine
C
Pintilie
M
M
Payne
David
D
O'Sullivan
Brian
B
Cummings
Bernard J
BJ
Warde
Padraig
P
Liu
Fei-Fei
FF
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy / Q000821:virology*; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D017735:Virus Latency / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C067169:RPL22 protein, human