Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (p<0.001 for all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, and p<0.001). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.
Highlights
Non-Hodgkin’s lymphoma (NHL) is the third common malignancy out of all malignances of Egyptian patients; it is of high rank among cancers in each sex, where it accounts for 8.4% of estimated incidence with 8.7 age standardized rate (ASR) per 100.000 [1]
large T-antigen (L-TAG) can bind pRb promoting the activation of the E2F1 transcription factor, inducing the expression of genes required for the entry to the S phase [3]
In Egypt, the high incidence of NHL is possibly related to the exposure of population, at a young age, to various bacterial, parasitic, and viral infections which result in a sustained stimulation of the lymphoid system [1, 14]
Summary
Non-Hodgkin’s lymphoma (NHL) is the third common malignancy out of all malignances of Egyptian patients; it is of high rank among cancers in each sex, where it accounts for 8.4% of estimated incidence with 8.7 age standardized rate (ASR) per 100.000 [1]. Simian virus (SV40) induces malignant transformation in rodents and human cells. This transformation is induced by the large T-antigen (L-TAG), known to promote transformation by binding and inactivating tumor suppressor genes, such as p53 and pRb [3]. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, inducing the expression of genes required for the entry to the S phase [3]. E2F1, the founding member of the family, induces proliferation; both Rb-deficiency and ectopic expression of E2F1 in normal cells lead to high level of apoptosis owing to its ability to activate a large number of proapoptotic genes through a plethora of distinct apoptotic mechanisms [6]. SV40 and E2F1 are coplayers in this malignancy or not, and correlate the results with the standard clinicopathological and survival data
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