Epstein-Barr virus infection and P53 expression in HIV-related oral large B cell lymphoma.
BACKGROUND
Head and neck non-Hodgkin's lymphomas in HIV positive patients are highly related with Epstein-Barr virus (EBV) infection. In general, viral agents can alter p53 protein levels by enhancing degradation of cellular p53 or by increasing its half-life by viral protein-p53 interaction. Moreover, it has been reported that modifications of p53 gene can modulate tumor cells' response to radio- and chemotherapy.


METHODS
To assess a possible role of EBV infection, p53 protein deregulation, and p53 gene alterations in exons 5 to 8, we have studied six cases of HIV-related primary oral large B-cell lymphoma. We used in situ hybridization (ISH) for EBV-DNA and EBV-encoded nuclear RNA-1 (EBER-1), immunohistochemistry (IHC) for EBV latent membrane protein -1 (LMP-1) and p53 proteins expression, and single strand conformational polymorphism (SSCP) analysis to screen p53 gene mutations in exons 5 to 8.


RESULTS
The EBV-DNA was present in all specimens, according to conventional DNA-ISH. No evidence for EBER-1 was found by ISH. The presence of EBV-DNA was correlated with the LMP-1 expression in all but one case. Moreover, p53 protein expression was negative in three cases and strongly positive in the others. However, mutational analysis of p53 gene in exons 5-8 showed no alteration.


CONCLUSIONS
Our data may suggest that both EBV infection and LMP-1 expression may cause p53 loss of function even in the absence of p53 gene mutations, as assessed by SSCP. We speculate that the presence of EBV-infection and p53 protein deregulation may be responsible for radio- and chemotherapy resistance, by influencing apoptosis of cancer cells.
Calzolari
A
A
Institute of Anatomic Pathology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Papucci
A
A
Baroni
G
G
Ficarra
G
G
Porfirio
B
B
Chiarelli
I
I
Di Lollo
S
S
D000328:Adult; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005091:Exons; D015870:Gene Expression; D016158:Genes, p53; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016483:Lymphoma, AIDS-Related / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism
D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins