Epstein-Barr virus infection, drug resistance and prognosis in Korean T- and NK-cell lymphomas.
T-cell lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. We tried to understand the effect of Epstein-Barr virus (EBV) on lymphogenesis, prognostic factors and drug resistance of T-cell lymphomas, and to establish their relationship with international prognostic factors. Formalin-fixed paraffin-embedded tissue sections from 35 patients (12 women and 23 men) with T-cell lymphomas were examined to detect the presence of EBV using RNA in situ hybridization for EBV-encoded small nuclear RNA (EBER) 1/2 and immunohistochemical stain for latent membrane protein (LMP)-1. We also tried to establish the expression of p53 and P-glycoprotein (P-gp) using immunohistochemistry. The distribution according to the subgroup was: two T-lymphoblastic lymphomas, 13 NK/T-cell lymphomas, one angioimmunoblastic T-cell lymphoma, 17 peripheral T-cell lymphomas, unspecified, and two anaplastic large cell lymphomas. The EBER was detected in 15 of 35 T-cell lymphomas (42.9%) and among these it was detected in five of 17 nodal lymphomas (29.4%) and 10 of 18 extranodal lymphomas (55.6%). There was close correlation between EBER positivity and NK/T-cell lymphoma (P = 0.032). Expression of LMP was found in a proportion of tumor cells in seven of the 15 EBER-positive cases (46.7%). There was no correlation between EBER expression and complete response (CR rate), but coexpression of EBER and p53 was associated with treatment failure (P = 0.047). The 18 patients (51.4%) with p53 expression had significantly poorer outcomes compared with the 17 patients without p53 expression (CR rate, P < 0.0005; overall survival, P = 0.0102). Twenty of 35 patients (57.1%) were positive for P-gp expression. P-gp expression was significantly associated with treatment failure (P = 0.001) and overall survival (P = 0.0089). Seventeen of 35 patients (48.6%) treated with systemic chemotherapy or radiation therapy achieved a CR after initial treatment. When the prognostic factors were grouped using the international prognostic index, the CR rate was 58.8% for the low risk group, 50.0% for the low-intermediate risk group, 14.3% for the high-intermediate risk group, and 0% for the high risk group. In conclusion, high incidence of EBV was detected among Korean patients with T-cell lymphomas. Our study supports the prediction that patients who express p53 and P-gp have a poorer prognosis than those who do not and this should be considered when treatment strategies for individual patients are selected.
Jung
C K
CK
Department of Clinical Pathology, St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Lee
K Y
KY
Kim
Y
Y
Han
K
K
Shim
S I
SI
Kim
B K
BK
Kang
C S
CS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007694:Killer Cells, Natural / Q000473:pathology / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53