Human Herpesvirus-8 Genes Are Expressed in Pulmonary Inflammatory Myofibroblastic Tumor (Inflammatory Pseudotumor)

Abstract

The presence of human herpesvirus-8 DNA sequences, as well as an overexpression of human interleukin-6 and human cyclin D1 in myofibroblastic cells of inflammatory myofibroblastic tumor (inflammatory pseudotumor), has recently been reported. We describe the pattern of human herpesvirus-8 gene expression in five cases of pulmonary inflammatory myofibroblastic tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR), with several positive and negative controls, was performed to detect mRNA of 11 open reading frames encoded by human herpesvirus-8 in lytic and latent stages of viral replicative cycle. We found molecular transcripts from ORF16, ORFK13, and ORF72 in the five cases and from ORFK2 in four of five neoplasms. The corresponding encoded proteins were human homologous oncoproteins (viral cyclin-D), inflammatory cytokines (viral IL-6), and inhibitors of apoptotic pathways (viral FLIP and viral Bcl-2), mostly expressed in a latent viral replicative stage. The rest of open reading frames examined included mainly lytic-associated genes and showed no expression. The spectrum of expressed viral genes is not the same as can be observed in Kaposi's sarcoma or multicentric Castleman's disease, suggesting that human herpesvirus-8 plays a different role in the pathogenesis of its associated diseases. These differences may be related to either cell-specific or immunologic host factors.

Absence of human herpesvirus-8 in pulmonary inflammatory myofibroblastic tumor: immunohistochemical and molecular analysis of 20 cases

“…Whereas the demographic, clinical, and histological features in all cases were typical for inflammatory myofibroblastic tumor, no viral DNA or latent nuclear antigen was identified utilizing immunohistochemical or molecular studies. The observations reported by Gó mez-Román et al, 10 were based on five cases of ALK-negative pulmonary inflammatory myofibroblastic tumor and raised the question of whether the presence of virus is restricted to the lesions lacking ALK expression Absence of HHV-8 in IMT F Tavora et al and/or to lesions of the lung (Table 3). In a subsequent report, Yamamoto et al 22 addressed this issue utilizing 21 ALK-positive and ALK-negative tumors from multiple sites including lung.…”

“…However, the Yamamoto et al study 22 had a limited number of pulmonary inflammatory myofibroblastic tumors, only three cases, and targeted only one ORF (ORF26). Similar to the study by Gó mez-Román et al, 10 we focused on pulmonary lesions and expanded the number of cases to 20, including 4 ALK-positive tumors; all 20 were negative for HHV-8. As we found no viral DNA, it was not surprising that all our cases were negative for latent nuclear antigen, corroborating the immunohistochemical findings on inflammatory myofibroblastic tumor from varying sites reported by Yamamoto et al 22 and pediatric cases reported by Mergan et al 23 Molecular identification of HHV-8 is known to produce both false-positive and false-negative results.…”

“…First, our detection system used four ORFs of the viral genome (Table 4), including two primer pairs that enabled detection of HHV-8 in the Gó mez-Román et al study, 10 namely ORFK2 (viral interleukin-6 homolog) and ORF72 (cyclin D homolog), a primer pair used in the Ding et al 27 study ORF26 (minor capsid protein), and another employed in several Kaposi sarcoma studies, that is, ORF16 (viral Bcl-2 homolog). Second, to increase efficiency of PCR amplification, the targeted sequences did not exceed 234 base pairs.…”

“…Gó mez-Román et al, 9 reported HHV-8 deoxyribonucleic acid (DNA) sequences in seven cases of inflammatory myofibroblast tumor, and also identified viral transcripts from several open reading frames (ORF). 10 In the English language literature, only three additional cases of pulmonary inflammatory myofibroblastic tumor have been studied for HHV-8 by immunohistochemical and molecular methods. 11 Thus, in the largest study to date, we investigated the presence of HHV-8 in pulmonary inflammatory myofibroblast tumor.…”

Inflammatory Myofibroblastic Tumor Arising in the Pancreatic Head: a Rare Case Report

“…The etiology and cellular origin of IMT remains unknown. Human herpes viruses 3 and 8, Eikenella corrodens, and Epstein-Barr virus have been proposed as possible infectious triggers of the IMT [3,4]. The most common sites of involvement are the lungs, mesentery, and omentum [2].…”