mTOR Signalling Pathway-protein Expression in Post-transplant Cutaneous Squamous-cell Carcinomas Before and After Conversion to mTOR-inhibitors

Anticancer Res. 2018 Jun;38(6):3319-3322. doi: 10.21873/anticanres.12597.

Abstract

Background/aim: Inhibitors of the mammalian target of rapamycin (mTORis) exert immunosuppressive and antitumor effects and are used in organ-transplant recipients (OTR) as immunosuppressants able to reduce skin tumor burden. This study investigated the effects of mTORis on the expression of mTOR pathway proteins in cutaneous squamous-cell carcinomas (SCC) developing in OTR, before and after switching to mTORis.

Materials and methods: An immunohistochemical study was performed on 23 SCC sections excised from OTR with post-transplant SCC, before or after switch to mTORis, with antibodies against pAkt, pmTOR and PI3K.

Results: pmTOR expression was found in 8/12 SCC pre-switch, and in 8/11 SCC post-switch, to mTORis. All (but 2) SCC expressed PI3K, and all SCCs expressed pAkt.

Conclusion: mTORis do not significantly change the immunohistochemical expression of molecules upstream of the mTOR inhibition (pmTOR, PI3K, pAkt), in cutaneous SCC.

Keywords: PI3K; immunohistochemistry; mTOR signaling; organ transplant recipients; pAkt; pmTOR; skin; squamous-cell carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / therapeutic use
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Sirolimus / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors
  • Transplantation / methods

Substances

  • Immunosuppressive Agents
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Sirolimus