Epstein-Barr Virus-Latent Membrane Protein 1 Expression Has a Favorable Influence in the Outcome of Patients with Hodgkin's Disease Treated with Chemotherapy

Abstract

The effect of molecular factors in the outcome of Hodgkin's Disease (HD) is being currently studied. In a previous series of HD, including patients treated only with radiotherapy and patients treated with chemotherapy (with or without radiotherapy), we found that a high proliferation index had an adverse influence in overall survival (OS) and in the achievement of a complete remission (CR). Loss of Rb expression also had an adverse prognostic influence in achievement of CR. On the other hand LMP1-EBV expression had a favorable influence for OS. The expression of other molecular factors, p53, bcl2 and CD15 did not show prognostic influence. In the present paper we have studied the effect of these molecular variables in 110 patients, of the previous series who had been treated with chemotherapy. A retrospective study was performed in these 110 patients with HD treated with chemotherapy (ABVD or variants, 62%, or regimes not containing adriamycin, 38%) with or without adjutant radiotherapy, collected at the 11 centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. The prognostic value of clinical variables and the expression of p53, bcl2, CD15, Rb, LMP 1-EBV and proliferative fraction demonstrated with sensitive immunohistochemical methods were studied. Cox's multivariate analysis was performed to assess their influence in failure-free survival (FFS) and OS. A multivariate logistic regression analysis was performed for studying the effect of the variables in the achievement of a CR. Of the clinical variables, only advanced stage (III/IV) had a significant independent adverse influence in FFS, in OS and in the achievement of CR and advanced age in OS. Of the molecular variables, LMP1-EBV had an independent and strong favorable influence in FFS, in OS and in the achievement of CR. Rb expression had a modest favorable influence in CR. The rest of the molecular variables had no independent influence on the outcome of the disease. In conclusion these results confirm the favorable prognostic value of LMP1-EBV expression in the subset of patients with HD treated with chemotherapy.

Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis

“…LMP-1 can also upregulate expression of epidermal growth factor receptor (EGFR) (Miller et al, 1995), which may then modulate expression of specific STATs upon ligand stimulation (Petersen and Haldosen, 1998;Kloth et al, 2002;Leong et al, 2002). Interestingly, in line with our findings, despite the fact that LMP-1 of EBV is known for its transforming ability and promotes cellular proliferation in various studies (Baichwal and Sugden, 1988;Kaye et al, 1993), tumours with LMP-1 expression tend to have better prognosis in EBV-associated malignancies such as Hodgkin's disease (Montalban et al, 2000;Glavina-Durdov et al, 2001) and NPC (Hu et al, 1995). Regarding the intimate association between STATs and NPC, further clarification of the relation between STAT signalling and the gene expression pattern of EBV may shed light on the pathogenesis of this unique malignancy and might have future therapeutic applications.…”

Epstein‐Barr virus‐encoded latent membrane protein 1 promotes stress‐induced apoptosis upstream of caspase‐2‐dependent mitochondrial perturbation

“…Indeed, expression of LMP1 was suggested to exert a favourable influence on the outcome of chemotherapeutic treatment of patients with Hodgkin's disease. 50 Similarly, we have shown that the expression of LMP1 correlates with a better prognosis of NPC in a Chinese population; in contrast, LMP1-negative NPCs recurred at a higher frequency and had an increased tendency to metastasize. 3 These findings are in line with the current observation that LMP1 potentiates apoptosis instigated by chemotherapeutic agents such as etoposide and cisplatin, both in HeLa cells and in the NPC-derived cell line, TW03.…”

Tumor-Infiltrated Immune Response Correlates with Alterations in the Apoptotic and Cell Cycle Pathways in Hodgkin and Reed-Sternberg Cells

“…Previous studies have described alterations in genes controlling apoptosis and proliferation of H/RS cells, such as p53 expression (3,4), deregulation of the Bcl2 family (3 -5), proliferative and/or apoptotic indices (3,6), activation of the nuclear factor-nB (NF-nB) pathway (7), and biological factors such as EBV detection (8,9), which influence the clinical aggressiveness of HL (5, 10 -12).…”