title: Role of HHV-8 and mTOR pathway in post-transplant Kaposi sarcoma staging.
abstract: Kaposi's sarcoma (KS) is one of the most frequent transplant related tumors. Several pathways are involved; however, the impact of the molecular phenotype associated to the tumor stage and the behavior-depending resultant therapy is still unknown. The aim of our study was to analyze the role of HHV-8 and mTOR pathway in tumor stages of skin KS after renal transplantation. Twelve renal transplant recipients with cutaneous KS from five transplant centers (1980-2007) under reduction of immunosuppression or conversion to mTOR inhibitor were included. The expression of HHV-8, PTEN, TGFβ, VEGF, phospho-mTOR, and phospho-P70S6K in tumoral tissue was analyzed. KS lesions were classified as patch, plaque, and nodule state. HHV-8 infection was found in all tissue samples. KS lesions showed high activation of VEGF, p-mTOR and p-P70S6K, low PTEN, and null TGFβ expression. The only pathway activated in a staging-dependent manner was mTOR with higher p-mTOR and p-P70S6K expression in nodule versus patch stage. KS lesions disappeared after 5.24 months in all converted patients without any recurrence in 14.05 years of mean follow-up. The activation of mTOR pathway according to KS stages supports the rational of the mTOR inhibitor in post-transplant Kaposi.
authors.affiliation: Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Astrid
authors.initials: A
authors.lastname: Hernández-Sierra
authors.affiliation: Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rovira
authors.affiliation: Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Petit
authors.affiliation: Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moya-Rull
authors.affiliation: Department of Nephrology, Hospital Universitario Puerta del Mar, Cadiz, Spain.
authors.forename: María Auxiliadora
authors.initials: MA
authors.lastname: Mazuecos
authors.affiliation: Department of Nephrology, Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Sánchez-Fructuoso
authors.affiliation: Department of Nephrology, Clínica Universitaria de Navarra, Pamplona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Errasti
authors.affiliation: Department of Pathology, Clínica Universitaria de Navarra, Pamplona, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Idoate
authors.affiliation: Renal Transplant Unit, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Josep María
authors.initials: JM
authors.lastname: Cruzado
authors.affiliation: Department of Pathology, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Fritz
authors.initials: F
authors.lastname: Diekmann
authors.affiliation: Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Oppenheimer
authors.affiliation: Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.affiliation: Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain.|Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Revuelta
mesh_terms: D000368:Aged; D005260:Female; D006085:Graft Survival; D019288:Herpesvirus 8, Human; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000821:virology; D013030:Spain; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: post-transplant malignancy; rapamycin