Role of HHV-8 and mTOR pathway in post-transplant Kaposi sarcoma staging
Hernández-Sierra A (1,2), Rovira J (2), Petit A (3), Moya-Rull D (2), Mazuecos MA (4), Sánchez-Fructuoso AI (5), Errasti P (6), Idoate MÁ (7), Cruzado JM (8), Vidal A(9), Diekmann F (1,2), Oppenheimer F (1,2), Campistol JM (1,2), Revuelta I (1,2).
(1) Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Spain.
(2) Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic - IDIBAPS, Barcelona, Spain.
(3) Department of Pathology, Hospital Clínic de Barcelona, Spain.
(4) Department of Nephrology, Hospital Universitario Puerta del Mar, Cadiz, Spain.
(5) Department of Nephrology, Hospital Clinico San Carlos, Madrid, Spain.
(6) Department of Nephrology, Clínica Universitaria de Navarra, Pamplona, Spain.
(7) Department of Pathology, Clínica Universitaria de Navarra.
(8) Renal Transplant Unit, Hospital Universitari de Bellvitge, Barcelona, Spain.
(9) Department of Pathology, Hospital Universitari de Bellvitge, Barcelona, Spain.
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 are 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 posttransplant Kaposi.
CITATION Transpl Int. 2016 May 21. doi: 10.1111/tri.12800