LANA-1, Bcl-2, Mcl-1 and HIF-1alpha protein expression in HIV-associated Kaposi sarcoma.
Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether the tissue viral load is a marker of KS progression is still unclear. Little is known about the level of expression of apoptosis-regulating proteins and of hypoxia-inducible factors (HIFs) in KS tumour cells relative to HHV8 expression. We therefore investigated the expression of the latency-associated nuclear antigen (LANA-1) of HHV8, Bcl-2, Mcl-1, Bax, Bcl-xL, caspase 3 and HIF-1alphain KS tissue specimens at different stages of the disease. The expression of these proteins was evaluated immunohistochemically using tissue microarrays (TMAs) in tissue specimens from 245 HIV-positive patients at different stages of the disease. Both LANA-1 and HIF-1alpha were expressed in KS biopsies taken at different stages, but their level increased throughout tumour progression. Additionally, the levels of Bcl-2 and Mcl-1 were higher in visceral KS lesions compared to levels observed in cutaneous and mucosal KS. This study demonstrates that late tumour stages of KS in tissues from HIV-positive patients are associated with high levels of LANA-1, HIF-1alpha and of the anti-apoptotic proteins, Bcl-2 and Mcl-1. Finally, the expression of these proteins can be potentially used as a tissue biomarker in defining patients with a higher risk of disease progression.
Long
E
E
Laboratory of Clinical and Experimental Pathology, Louis Pasteur Hospital, Nice 06002, France.
Ilie
M
M
Hofman
V
V
Havet
K
K
Selva
E
E
Butori
C
C
Lacour
J P
JP
Nelson
A M
AM
Cathomas
G
G
Hofman
P
P
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009687:Nuclear Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D000956:Antigens, Viral; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C109540:latency-associated nuclear antigen