Bone marrow that is positive for Epstein-Barr virus encoded RNA-1 by in situ hybridization is related with a poor prognosis in patients with extranodal natural killer/T-cell lymphoma, nasal type.
OBJECTIVE
Extranodal NK/T-cell lymphoma, nasal type is an aggressive lymphoma that is always associated with Epstein-Barr virus (EBV). This study was done to evaluate the use of EBV-encoded RNA-1 in situ hybridization (EBER-1 ISH) to detect occult micrometastasis in the bone marrow (BM) of patients with nasal NK/T-cell lymphoma.


METHODS
A total of 23 patients who underwent BM biopsy for routine pre-therapeutic evaluation were enrolled in the study. We used EBER-1 ISH to investigate the expression of EBER-1 in 30 BM specimens. The clinical correlation and therapeutic outcomes of these patients were analyzed. In addition, genomic analysis of EBV was performed in five patients.


RESULTS
Conventional morphologic examinations failed to identify any lymphoma involvement in the 23 BM specimens obtained at initial staging. However, 10 of the 23 BM were positive for EBER-1. A lower survival rate was seen in patients with BM positive for EBER-1. Only the BM EBER-1 ISH result was shown to be an independent variable predicting overall survival in stage I and II patients (p=0.027; hazard ratio for death 0.066, 95% confidence interval, 0.006 to 0.733), suggesting that EBER-1 positivity in BM is the major determinant of a poor prognosis. However, discrepancies in the EBV strains between the primary tumor and BM existed in two of the five studied patients.


CONCLUSIONS
We suggest that EBER-1 ISH should be performed on BM specimens of patients with nasal NK/T-cell lymphoma to identify the presence of EBER-1 positive cells, which appears to carry a poor prognosis. Whether or not the EBER-1 positive cells in the BM of nasal NK/T-cell lymphoma patients are true tumor cells requires further study.
Huang
Wen-Tsung
WT
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 1 Doshiue Road, Tainan 701, Taiwan, Republic of China.
Chang
Kun-Chao
KC
Huang
Guan-Cheng
GC
Hsiao
Jenn-Ren
JR
Chen
Helen-H W
HH
Chuang
Shih-Sung
SS
Chen
Tsai-Yun
TY
Su
Wu-Chou
WC
Tsao
Chao-Jung
CJ
D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000473:pathology* / Q000821:virology*; D017931:DNA Primers; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012367:RNA, Viral / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis
D017931:DNA Primers; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral