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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1109-1110
CORRESPONDENCE
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Letter |
To the editor:
Detection of vascular endothelial growth factor in AIDS-related
primary effusion lymphomas
Primary effusion lymphoma (PEL), an infrequent type of
AIDS-related non-Hodgkin's lymphoma involving B lymphocytes infected with Kaposi's sarcoma-associated herpesvirus (KSHV) and often Epstein-Barr virus, is characterized by lymphomatous effusions in the
pleural or abdominal cavity, usually without an identifiable tumor
mass.1,2 Recently, liquid growth of PEL-derived cell lines
in the peritoneal cavity of immunodeficient mice was found to require
the presence of vascular endothelial growth factor (VEGF),3
an angiogenesis factor that is also a potent inducer of vascular
permeability.4,5 Based on these results suggesting a role
for VEGF in the pathogenesis of PEL, we measured levels of VEGF in PEL
effusions from patients with AIDS and compared them to those in other
malignant and nonmalignant effusions.
Samples from 8 AIDS-PEL effusions (2 pleural, 1 pericardial and 5 peritoneal) were obtained from the AIDS Malignancy Bank (National
Cancer Institute, Bethesda, MD) and from clinical samples collected in
our institutes. Control pleural, peritoneal, or pericardial fluids were
obtained from 4 AIDS patients with inflammatory effusions without PEL,
5 HIV-negative patients with nonmalignant effusions, 8 patients with
ovarian cancer, 5 patients with lung cancer, 1 patient with breast
cancer, and 2 patients with thymic cancer. The concentrations of VEGF
were measured by enzyme-linked immunosorbent assay (R&D Systems,
Minneapolis, MN). All AIDS-PEL effusions had measurable VEGF
(Figure). In AIDS PEL effusions, VEGF
levels (median 3977 pg/mL; range 1133-11417 pg/ml) were higher than in
AIDS effusions without PEL (median 175 pg/mL; range <15-484 pg/mL;
P < .02, Student t test), other nonmalignant
effusions (median 137 pg/mL; range <15-303 pg/mL;
P < .02), and in lung/breast/thymic malignant effusions (median 969 pg/mL; range <15-2993 pg/mL; P < .05). VEGF
levels in malignant ovarian effusions (median 5098 pg/mL; range
574-11091 pg/mL) were comparable to those in AIDS PEL effusions
(P = .595).
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VEGF levels in effusions from patients with malignant and
nonmalignant disease.
AIDS-PEL (n = 8), nonmalignant AIDS, no PEL (n = 4), ovarian cancer
(n = 8), lung cancer (n = 5; open circles), breast cancer (n = 1;
open square), thymic cancer (n = 2; closed circles) and nonmalignant
samples (n = 5). Bars indicate the average of each group. Statistical
significance versus AIDS-PEL was determined by Student t test
analysis.
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It was previously reported that levels of VEGF in malignant ascites are
generally higher than in nonmalignant effusions, with wide variations
noted depending on the nature of the malignancy.4,5 Tumors
of sarcoma and carcinoma origin have been reported to produce substantially more VEGF than hematological tumors.4
Malignant ascites from ovarian cancers were found to contain some of
the highest levels of VEGF, on the average 45-fold higher than in nonmalignant controls.5 Here we show that levels of VEGF in PEL effusions are comparable to those in malignant ovarian effusions.
Compared to normal or other malignant lymphocytes, PEL cells have
markedly reduced expression of several adhesion molecules.1 This defect may prevent PEL cell anchorage and subsequent development of solid tumors. By promoting vascular leakage, VEGF may contribute to
PEL liquid growth in body cavities. In mice, VEGF neutralization prevented the establishment of PEL ascites. Patients with PEL, usually
with advanced AIDS, have displayed a median survival of only 3 months
even with administration of chemotherapy.3 Neutralization of VEGF in PEL effusions may represent a rational and novel therapeutic approach not likely to further compromise patient immune status.
Yoshiyasu Aoki
Giovanna Tosato
Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, MD, USA
Yoshihiro Nambu
Department of Internal Medicine, Kanazawa Medical
University, Ishikawa, Japan
Aikichi Iwamoto
Institute of Medical Science, University of Tokyo, Tokyo,
Japan
Robert Yarchoan
HIV and AIDS Malignancy Branch, Division of Clinical
Sciences, National Cancer Institute, National Institute of
Health, Bethesda, MD, USA
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References |
1.
Boshoff C, Gao SJ, Healy LE, et al.
Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice.
Blood.
1998;91:1671-1679[Abstract/Free Full Text].
2.
Cesarman E, Knowles DM.
The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases.
Semin Cancer Biol.
1999;9:165-174[Medline]
[Order article via Infotrieve].
3. Aoki A, Tosato G. Role of Vascular Endothelial Growth Factor/Vascular
Permeability Factor in the Pathogenesis of KSHV-Infected Primary
Effusion Lymphomas. BLOOD. In press.
4.
Luo JC, Yamaguchi S, Shinkai A, Shitara K, Shibuya M.
Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors.
Cancer Res.
1998;58:2652-2660[Abstract/Free Full Text].
5.
Zebrowski BK, Liu W, Ramirez K, Akagi Y, Mills GB, Ellis LM.
Markedly elevated levels of vascular endothelial growth factor in malignant ascites.
Ann Surg Oncol.
1999;6:373-378[Medline]
[Order article via Infotrieve].
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