Role of HHV-8 and mTOR pathway in post-transplant Kaposi sarcoma staging

Transpl Int. 2016 Sep;29(9):1008-16. doi: 10.1111/tri.12800. Epub 2016 Jul 7.

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.

Keywords: post-transplant malignancy; rapamycin.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Female
  • Graft Survival
  • Herpesvirus 8, Human
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging / methods*
  • PTEN Phosphohydrolase / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / virology
  • Spain
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Immunosuppressive Agents
  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human