Evidence for a Multiclonal Origin of Multicentric Advanced Lesions of Kaposi Sarcoma

Autor: Renan Duprez, Oumkaltoum Hbid, Antoine Gessain, Michel Huerre, Jean-Louis Essame Oyono, Patricia Tortevoye, Blaise Nkegoum, Marie-Jeanne Lando, Dominique Sainte-Marie, Josette Brière, Pierre Couppié, Eric Kassa-Kelembho, Céleste Lebbé, Vincent Lacoste, Camille Francès, Antoine Mahé
Přispěvatelé: Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Service de Médecine et d'Anatomopathologie, CHU de Yaoundé, Service d'Anatomopathologie, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Maroc, Institut d'Hygiène Sociale, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Histotechnologie et Pathologie, Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital de Cayenne, CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Rok vydání: 2007
Předmět:
Male
Cancer Research
Pathology
viruses
MESH: Aged
80 and over

0302 clinical medicine
MESH: Child
Gammaherpesvirinae
Child
Lymph node
Skin
Aged
80 and over

MESH: Aged
0303 health sciences
MESH: Middle Aged
medicine.diagnostic_test
Middle Aged
Viral Load
3. Good health
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Herpesvirus 8
Human

Monoclonal
Female
Sarcoma
MESH: Viral Load
Viral load
Adult
medicine.medical_specialty
Adolescent
Biology
03 medical and health sciences
MESH: Skin
Biopsy
medicine
Humans
Sarcoma
Kaposi

Aged
030304 developmental biology
MESH: Adolescent
MESH: Herpesvirus 8
Human

MESH: Humans
MESH: Clone Cells
Cancer
MESH: Adult
medicine.disease
biology.organism_classification
MESH: Male
Clone Cells
MESH: DNA
Viral

Tonsil
DNA
Viral

MESH: Sarcoma
Kaposi

MESH: Female
Zdroj: JNCI Journal of the National Cancer Institute
JNCI Journal of the National Cancer Institute, 2007, 99 (14), pp.1086-94. ⟨10.1093/jnci/djm045⟩
JNCI: Journal of the National Cancer Institute
JNCI: Journal of the National Cancer Institute, 2007, 99 (14), pp.1086-94. ⟨10.1093/jnci/djm045⟩
ISSN: 1460-2105
0027-8874
DOI: 10.1093/jnci/djm045
Popis: International audience; BACKGROUND: Kaposi sarcoma (KS) is a complex tumor of uncertain clonality. Studying the viral clonality of the human herpesvirus 8 (HHV-8) in KS to determine clonality of the tumors, a strategy that has been used previously with Epstein-Barr virus and its associated tumors, may elucidate whether multicentric (disseminated) KS lesions correspond to metastatic lesions or to expansions of independent clones. METHODS: A series of 139 KS biopsies (from skin, lymph node, or tonsil) was obtained from 98 patients, with 59 biopsies from 18 patients with disseminated multicentric KS skin lesions. The degree of spindle cell infiltration in biopsies was established by direct observation of hematoxylin-eosin-stained sections, and HHV-8 viral load was quantified by real-time polymerase chain reaction. To determine cellular clonality, the size heterogeneity of the HHV-8-fused terminal repeat (TR) region was determined by probing of electrophoresed restricted genomic DNA from KS biopsies for the HHV-8 TR sequence. RESULTS: HHV-8 clonality analysis was performed on the 62 samples for which sufficient DNA was obtained. Most samples corresponded to histologically nodular lesions with high spindle cell infiltration and high viral load. A clonal HHV-8 pattern was determined for 59 samples; 11 were found to be monoclonal and 48 to be oligoclonal. The informative samples that were from disseminated KS skin lesions (n = 26, from six patients) were either monoclonal or oligoclonal, and the size of HHV-8 episomes varied between these samples. CONCLUSION: Although some tumor KS lesions were monoclonal expansions of HHV-8-infected spindle cells, most advanced lesions were oligoclonal proliferations. Furthermore, individual KS disseminated tumor skin lesions were found to represent distinct expansions of HHV-8-infected spindle cells. Thus, our results suggest that KS lesions, especially in patients with advanced skin tumors, are reactive proliferations rather than true malignancies with metastatic dissemination.
Databáze: OpenAIRE