ABSTRACT
Background: The number of viruses associated with lymphoma has increased in the last 20 years. Several studies from different parts of the world have indicated a potential association between a variety of lymphoproliferative disorders and viruses, as hepatitis C virus [HCV] hepatitis B virus [HBV] and Epstein-Barr Virus [EBV]
Aim of the work: The aim of this work was to study the role of oncogenic viruses in patients with malignant Non Hodgkin's lymphoma [NHL], also, to study the correlation of different subtypes of B cell-NHL and the viruses detected
Patients and methods: Twenty cases of B cell-NHL were investigated for serum HCVAbIgG, HBsAg by Elisa technique. Also HCV-RNA sequences as well as HBV-DNA and EBV-DNA sequences were detected in the tumor tissues by using RT-PCR. HCV is also examined by immunohistochemical method. In addition 10 cases of non neoplastic lymphadenopathy were taken as a control
Results: Out of the 20 B cell-NHL patients 6 [30%] cases showed positive HCV AbIgG, and 8 [40%] cases showed positive HBSAg in their sera. In four cases out of the 6 HCV positive patients, HCV-RNA sequences were detected by PCR, and in 7 patients out of the 8 HBV positive patients, HBV-DNA sequences were present. 5 [25%] out of the 20 cases were negative for both HBV-DNA and HCV-RNA sequences. EBV was positive in all B cell-NHL cases by EBNA gene while it was detected in 9 [45%] out of the 20 NHL cases by LYDMA gene. A coinfection was detected between HCV and EBV in 2 cases out of the 6 HCV positive cases, and between HBV and EBV in 3 out of the 7 HBV positive cases. Two cases were positive for EBV only, and negative for both HCV and HBV sequences. All control cases were positive for polyclonal EBV and negative for HCV-RNA and HBV-DNA sequences, 3 [15%] cases out of the 20 cases of B cell-NHL showed positive staining in the tissues for HCV-Abs by immunohistochemical method. All positive cases of the studied viruses showed no predilection for a particular subtypes of B-cell NHL
Conclusion: A significant association was present between HBV, EBV and B cell-NHL [P= 0.05 and 0.043 respectively] and the association between HCV and B cell-NHL is not significant. This raised the possibility that these viruses may play an etiologic role in the induction of B cell-NHL disease. No relation was found between the different histological subtypes of NHL and the viruses detected
ABSTRACT
Kaposi's sarcoma [KS] is a multifocal angioproliferative disease characterized by the proliferation of spindle-shaped cells predominantly of vascular origin considered to be the neoplastic element of KS, neoangiogenesis, inflammatory cell infiltration and oedema. The presence of high levels of inflammatory cytokines [IC] such as IFN, TNF, IL-1, IL-6 and angiogenic molecules mediates lesion formation. Recently a new viral agent termed human herpes virus-8 [HHV-8] also known as Kaposi's sarcoma associated herpes virus [KSHV] has been found in all forms suggesting a common etiopathogenesis for all forms of KS. Human IL-6, [H-IL6] is a multifunctional cytokine that acts on a wide variety of cells, serves as a growth factor for myeloma and plasmocytoma cells. Bcl[2] is a proto-oncogene known to prolong survival of quiescent non proliferating cells by inhibiting the process of programmed cell death. KSHV contains a gene that has functional and sequence homology to the apoptotic Bcl[2] family of proteins. The PCNA is now recognized as one of the key proteins in DNA metabolic events because of its direct interactions with many proteins involved in important cellular processes. The aim of this study was to acertain the value of HHV-8 DNA sequences in routinely processed, formalin fixed embedded tissues as a cause of KS and to estimate the level of human interleukin-6 [H-IL-6] in its different stages with or without HIV seropositive case. This study also aimed at evaluating the expression of Bcl2 and PCNA in the progressive stages of KS and highlight their role in this progression
Patients and Method: 20 cases of KS [17 classical KS and 3 AIDS related KS] with 8 plaque stage [group I] and 12 nodular [group II] were tested for HHV-8 DNA sequences by PCR assay, conventional H and E staining for histopathological diagnosis. Immunohistochemical staining of Bcl[2] and PCNA on paraffin fixed embeded tissue. Blood samples were taken from all patients as well as from 10 control subjects for estimation of H-IL-6 by immunoassay
Results: Human herpes virus 8 - DNA was detected in 16 out of the 20 [80%] formalin fixed embedded tissue sections. All nodular lesions [group II] were found to be positive for HHV-8 [100%]. While 50% of the plaque lesions were positive for HHV-8 [group I]. All HIV cases [n=3] [100%] previously described were also positive for HHV-8 and belonged to the nodular stage [group III]. The mean value of serum HIL-6 in the 16 cases were [10.23+/2.9 pg/ml], and in group I [plaque stage] was [7.5 +/ 1.3 pg/ml]. In group II [nodular stage] was [11.1 +/ 1.9 pg/ml]. Whereas in group III [nodular stage with seropositive HIV] was 14.4 +/ 1.9 pg/ml]. The mean value in the control group was [3.27 +/ 0.72 pg/ml]. There is highly significant difference between group I and group II [P = 0.0001] compared to the control group but, no statistically significant differences were found between group I or II and group III. The relation between H-IL-6 levels and HHV-8 DNA in paraffin embedded tissue was statistically significant [P= 0.045]. This study also showed 4 cases in plaque stage [50%] were negative for HHV-8 but still their mean value of H-IL-6 was [10.5 +/ 3.9 pg/ml] which is significant to the control group [P= 0.045]. No significant relation was detected between H-IL-6, and the different parameters [Bcl[2], PCNA, and sex]. Bcl[2] positivity was detected in 70% of studied cases. Bcl[2] immunoexpression increased from plaque stage [28.67%] to the nodular stage [71.4%] and this relation was statistically significant [P=0.046] 75% of HHV-8 positive cases showed Bcl[2] positivity and this relation was also statistically significant. [P=0.039]. PCNA immunohistochemical expression was detected in 80% of studied cases PCNA labeling index [PCNA LI] was grade 1, in 20%, grade 2 in 35% and grade 3 in 45% of studied cases. No statistical significant relation was detected between PCNA LI and chemical stage, or HHV-8 positivity. All AIDS associated KS were Bcl[2] positive and showed grade 3 PCNA LI and inspite of the fact that this relation were statistically significant in both, the small number of AIDS positive cases [3 cases] made this statistical significant not reliable