Epstein-Barr virus LMP1 status in relation to apoptosis, p53 expression and leucocyte infiltration in nasopharyngeal carcinoma.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection. EBV-encoded LMP1, expressed in most of NPC, has been suggested to have an important role in the pathogenesis and development of NPC and its expression correlates with poor prognosis.


METHODS
Eighty-seven NPC biopsies were analyzed by immunohistochemistry for expression of markers of cell proliferation, apoptosis, infiltrating T lymphocytes and macrophages in relation to the LMP1 status.


RESULTS
Our findings indicate that the p53 accumulation in NPC was significantly correlated to LMP1 and MMP9 overexpression in NPC cells. The frequency of apoptotic cells in NPC, as analyzed by TUNEL labeling, correlated to Fas-L and caspase-3 expression, and inversely to LMP1, p53 and MMP 9 expression. CD8+ T cell infiltration was predominately seen in nests of cancer cells with a high level of EBV-LMP1 expression, but these CD8+ T cells showed low expression of CD25 and TIA-1, indicating that they were not activated.


CONCLUSIONS
Our observation suggests that the heavy infiltration by lymphocytes in LMP1-positive NPC tumors does not appear to counteract tumor growth by cytoxicity as indicated by the low apoptotic index. Thus, LMP1 seems to enhance survival- and proliferation-related signals in NPC. In analogy with other tumors, both the infiltrating T cells and the accumulated p53 may be inactive.
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Jian-Yong
JY
Shao
Ingemar
I
Ernberg
Peter
P
Biberfeld
Thomas
T
Heiden
Yi-Xin
YX
Zeng
Li-Fu
LF
Hu
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D012367:RNA, Viral / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014763:Viral Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D019394:Ki-67 Antigen; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins; D020780:Matrix Metalloproteinase 9