Lymphatic and vascular origin of Kaposi's sarcoma spindle cells during tumor development.
The histogenesis of Kaposi's sarcoma (KS) tumor spindle cells (SC) remains controversial but several immunohistochemical studies favor a lymphatic origin. Twenty KS surgical biopsies were analyzed for the coexpression of LANA, CD34, LYVE-1, D2-40, VEGFR-2, VEGFR3 by using double or triple immunostaining. Most of the SC in both early and late KS expressed the lymphatic markers LYVE-1, D2-40 and VEGFR-3 and the blood vascular endothelial/endothelial precursor cell markers CD34 and endothelial stem cell marker VEGFR-2. All the LANA+ SC in early and late KS were LYVE-1+, but only 75% of these LANA+ cells were CD34(+). The CD34(+)/LANA+ cells increased from early- (68.8%) to late-stage KS (82.2%). However, approximately 18% of the LANA+ SC in early KS were CD34(-) but were LYVE-1+, suggesting that resident lymphatic endothelial cells (LEC) are targeted for primary infection by human herpesvirus-8. This LANA+/LYVE-1+/CD34(-) (resident LEC) cell population clearly decreased during the development of KS from early (18.7%) to late KS (2.9%). Thus, in late stages of KS, most SC were LANA+/CD34(+)/LYVE-1+. However, in both early- and late-stage KS, approximately 18% of the SC were CD34(+)/LANA-/LYVE-1 -- and could represent newly recruited endothelial precursor cells, which become infected in the lesion and eventually undergo a phenotype switch expressing LEC markers. Our study apparently indicates that KS represents a unique variant of tumor growth with continues recruitment of tumor precursor cells as well as proliferation and decreased apoptosis of SC.
Pyakurel
Pawan
P
Department of Pathology and Oncology, Karolinska Institute/Hospital, S-17176 Stockholm, Sweden. pawan.pyakurel@ki.se
Pak
Fatemeh
F
Mwakigonja
Amos R
AR
Kaaya
Ephata
E
Heiden
Thomas
T
Biberfeld
Peter
P
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D004729:Endothelium, Lymphatic / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D019084:Fluorescent Antibody Technique, Indirect; D019288:Herpesvirus 8, Human / Q000472:pathogenicity; D006801:Humans; D042583:Lymphangiogenesis; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface