Loss of heterozygosity and its correlation with clinical outcome and Epstein-Barr virus infection in nasopharyngeal carcinoma.
Sixty-one human nasopharyngeal carcinomas (NPC) were examined by allelotype analysis for the purposes of detecting potential association between loss of heterozygosity (LOH), clinicopathological parameters and Epstein-Barr virus (EBV) infection. LOH was performed using 257 polymorphic markers on 22 chromosomes. High frequency LOH (> or = 60%) was observed on 12 chromosome arms including 1p, 2p, 2q, 3p, 3q, 5q, 9p. 9q, 11q, 13q, 14q and 17q, with the highest LOH frequency of 91% on 3p. Seventy-three loci presented LOH frequency > or = 30%; most of these loci clustered on 1p36 p34, 2p25-p24, 3p14-p21, 3p24-p26, 5q11-q14, 5q31-q33, 9p21-p23, 9q33-q34, 11q23-q25, 13q12 q14, 13q31-q33, 14q13-q11, 14q32 and 19q13. On 1p36-p34, 2p25-p24, 5q13-q11, 5q31-q33 and 19q13 are reported for the first time. LOH was correlated with specific clinicopathological parameters including tumor T-stage, N-stage, TNM-stage, tumor differentiation and serum antibody titers of IgA against virus capsid antigens (VCA) and early antigen (EA) of EBV in NPC (LOH frequency > or = 30%). Significantly high LOH frequency was observed on 9p21 (56%) and 19q13 (50%) in NPC with stage T3+T4, while significantly higher LOH frequency was observed on 12p11 (65%) in NPC with stage T1 + T2. Significantly higher LOHfrequency on 19q13 was also observed in NPC with advanced TNM-stage (III+IV). High fractional allelic loss (FAL) value and high antibody titers of EBV IgA/VCA and/or IgA/EA were significantly correlated with T3 + T4-stage, distant lymph node metastasis and advanced TNM-stage of NPC. We also found that NPC patients with high titers of IgA/VCA and IgA/EA showed high LOH frequency on 16q (48%) and 19q13 (48%). These results suggest that LOH on 9p21, l6q and 19q13 may be responsible for the aggressiveness and progression of NPC; there may be an interaction between allelic loss and EBV infection in the etiology of NPC. High frequency of LOH on 4q21 and 14q11-q12 were alsofound to be correlated with WHO type III NPC histopathology, suggesting that LOH on these regions may cause poor NPC differentiation. Our data also may be useful for the development of a NPC molecular staging system, a system which may augment the use of clinical pathological features in the diagnosis and prognosis of this disease.
Shao
J Y
JY
Department of Patholog, Sun Yat-Sen University of Medical Sciences, Guangzhou, China.
Huang
X M
XM
Yu
X J
XJ
Huang
L X
LX
Wu
Q L
QL
Xia
J C
JC
Wang
H Y
HY
Feng
Q S
QS
Ren
Z F
ZF
Ernberg
I
I
Hu
L F
LF
Zeng
Y X
YX
D000328:Adult; D000368:Aged; D000483:Alleles; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins; D002277:Carcinoma / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D002681:China / Q000453:epidemiology; D002877:Chromosomes, Human / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D005819:Genetic Markers; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D017384:Sequence Deletion; D016896:Treatment Outcome
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; C033305:Epstein-Barr virus early antigen; D005819:Genetic Markers; D007070:Immunoglobulin A