Assessment of the prognostic impact of the Epstein-Barr virus-encoded latent membrane protein-1 expression in Hodgkin's disease

We have examined expression of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) in the malignant Hodgkin and Reed-Sternberg (HRS) cells o f Hodgkin's disease (HD) and its impact on response to treatment and on sur vival. Paraffin tissue from 100 adult immunocompetent patients with HD were analysed using immunohistochemistry to identify LMP1 expression. According to the Rye classification, 8% of patients had lymphocyte predominance (LP) subtype, 48% had nodular sclerosis (NS) disease, 37% were of the mixed cel lularity (MC) subtype and 7% were of the lymphocyte depletion (LD) subtype. During the five year follow-up period 27 patients died and 74 patients ach ieved a complete remission. Patients with LD subtype were older (P = 0.03), less frequently achieved complete remission (P = 0.01), had shorter diseas e-free survival (P = 0.01) and overall survival (P = 0.002) compared with t he other subtypes of HD. LMP1 expression was found in the tumour cells of 2 6% of cases of HD. LMP1 expression was less common in NS disease than in th e other subtypes (P = 0.05), whereas an association between MC subtype and LMP1 expression was not found (P = 0.22). Using the log-rank test there wer e no differences in overall survival or disease-free survival based on EBV status either when all patients were analysed or when LD and LP subtypes we re excluded. However, the presence of EBV was associated with significantly longer disease-free survival in the subgroup of patients less than or equa l to 30 years old (P = 0.02) and in those patients less than or equal to 34 years old (P = 0.05). In contrast, there was a trend for shorter disease-f ree survival for EBV-positive patients in the subgroup > 35 years old, but this difference was not statistically significant (P = 0.11). A similar tre nd was observed in patients > 50 years old. Analysis of the impact of LMP1 expression in patients who had different stage and B symptoms status showed that expression of EBV was associated with longer disease-free survival (P = 0.019) in early stage (1 + 2) patients without B symptoms. Significant d ifferences in the other subgroups based on EBV status was not found. Factor s adversely affecting the likelihood to achieve a complete remission were: absence of LMP1 expression (OR 6.4, 95% CI 1.07-38.5, P = 0.04), age (OR 1. 68, 95%CI 1.15-2.5, P = 0.007) and subtype of HD (OR 3.32, 95%CI 1.11-9.94, P = 0.03). Age and subtype of HD had an independent impact on overall surv ival (P = 0.01). We conclude that expression of LMP1 in HRS cells has a fav ourable impact on prognosis for HD patients, but that this effect may be re stricted to young adult patients and those with early stage disease. (C) 20 01 Cancer Research Campaign.