Korean J Med.  2000 Feb;58(2):213-220.

Clinical significance of kaposi's sarcoma-associated herpesvirus(KSHV) infection in patients of multiple myeloma

• Kim CK
• Hong DS
• Park SK
• Lee GT
• Won JH
• Baick SH
• Lee DW
• Park HS

Abstract

BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) been shown to be associated with human diseases including Kaposi's sarcoma, pleural effusion lymphoma, multicentric Castleman's disease. The IL-6 may both stimulate myeloma growth and prevent apoptosis of malignant plasma cells. Interestingly, viral IL-6(vIL-6), homolog to human interleukin-6(IL-6) in KSHV genome retains biologic activity. Thus, oncogenic role of the KSHV has been proposed as a pathogenesis of the multiple myeloma. We used ISH to determine the frequency of patients with multiple myeloma and plasmacytosis associated with KSHV-infected BM cells in fresh core biopsies and to determine the correlation between KSHV infection and clinical characteristics.
METHODS
Bone marrow(BM) biopsy samples from 16 cases of multiple myeloma, 2 cases of monoclonal gammopathy of undetermined significance(MGUS) were obtained from the pathology division of Soon Chun Hyang University Hospital, Seoul, Korea. Biopsy sample of Kaposi's sarcoma for positive control and BM biopsy samples of myelodysplastic syndrome(MDS) and malignant lymphoma for negative control were obtained. Bitinylated probe to KSHV were prepared with the following sequences: 5' to 3' TGCAGCAGCTGTTGGTGTACCACATATCT. and in situ hybridization (ISH) was performed.
RESULTS
Among the 18 patients. Two patients were MGUS and among 16 patients with multiple myeloma, 1 in stage IB disease, 1 stage IIB disease, 8 stage IIIA disease, 4 stage IIIB diseases and 2 in variant of multiple myeloma, extramedullary plasmacytoma. Strong positive signal was detected in nuclei and cytoplasm of the malignant cells of biopsy sample from 1 cases of Kaposi's sarcoma by ISH(positive control). Signal was not detected in BM biopsy samples of 7 cases from MDS and malignant lymphoma(negative control). Among 16 patients with multiple myeloma, 15 demonstrated viral positive cells and 2 cases with MGUS also showed viral positive cells by ISH. Signal was detected in nuclei and cytoplasm of stromal cells. Signal was strongly detected in MGUS than multiple myeloma. Positivity of the KSHV was not related with stage of the patients with multiple myeloma. One patients with multiple myeloma was studied at diagnosis and after chemotherapy. After chemotherapy KSHV was not detected.
CONCLUSION
In MGUS and multiple myeloma, KSHV infects the stromal cells of BM rather than malignant plasma cells. On the basis of these data, we have supposed KSHV to play a role in transformation from MGUS to multiple myeloma. Particularly, due to the fact that signal of ISH was strongly detected in MGUS and was not detected in one case with multiple myeloma, it was presumed that KSHV was not major role in already advanced multiple myeloma but statistic significance was not demonstrated because of small numbers of cases. Further studies to reveal the correlation of KSHV and pathogenesis of multiple myeloma are needed.

Keyword

Multiple myeloma; Pathogenesis; KSHV; ISH

MeSH Terms

Apoptosis
Biopsy
Cytoplasm
Diagnosis
Drug Therapy
Genome
Giant Lymph Node Hyperplasia
Herpesvirus 8, Human
Humans
In Situ Hybridization
Interleukin-6
Korea
Lymphoma
Multiple Myeloma*
Paraproteinemias
Pathology
Plasma Cells
Plasmacytoma
Pleural Effusion
Sarcoma, Kaposi
Seoul
Stromal Cells
Interleukin-6