Abstract
BackgroundElectrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years.MethodsA total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12–48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification.ResultsAll KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10−7 to 6.9 × 10−4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response.ConclusionsECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.
Highlights
Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions
The aim of this study was to evaluate the effect of ECT on human herpesvirus type 8 (HHV8) viral load and the role of HHV8 latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/ K10.1, K10.5/K10.6 and ORF16) gene expression in tumour biopsies and peripheral blood mononuclear cells (PBMCs) from patients affected by classic KS with different response to ECT
This study included a total of 27 patients (24 males and 3 females) affected by classic KS, with a median age at the diagnosis of 74 years (Table 2)
Summary
Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. Kaposi sarcoma (KS) is a locally aggressive vascular tumour generally presenting with cutaneous multiple patches, plaques or nodules [1]. Epidemiological and clinical forms of KS comprise: 1) the classic or sporadic KS, mainly developing in elderly men of Mediterranean and Eastern European origin; 2) the African or endemic KS; 3) the iatrogenic or immunosuppression-associated KS; and 4) the epidemic or human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-related KS [2, 3]. More recently electrochemotherapy (ECT) has shown to be an effective local treatment for KS lesions [10]. ECT has shown to be very effective for the local treatment of cutaneous metastatic nodules and primary skin tumours including cutaneous KS [10, 13, 14]
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