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Published on: April 12, 2024
mTOR Signalling Pathway-protein Expression in Post-transplant Cutaneous Squamous-cell Carcinomas Before and After
Triantafyllia Koletsa1, Georgios Petrakis1, Georgia Karayannopoulou1
1Department of Pathology, AHEPA Hospital, Aristotelian University of Thessaloniki, Thessaloniki, Greece.
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.
Insights
Mammalian target of rapamycin inhibitors (mTORis) do not significantly alter key protein expression in cutaneous squamous cell carcinomas (SCC) of organ-transplant recipients. This suggests mTORis do not impact the mTOR pathway in these skin tumors.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Mammalian target of rapamycin inhibitors (mTORis) are used in organ-transplant recipients (OTR) for immunosuppression and to reduce skin tumor burden.
- Cutaneous squamous cell carcinoma (SCC) is a common concern in OTR.
- The effects of mTORis on SCC tumor biology in OTR require further investigation.
Purpose of the Study:
- To investigate the impact of mTOR inhibitors on the expression of key mTOR pathway proteins in cutaneous squamous cell carcinomas (SCC) from organ-transplant recipients (OTR).
- To compare the expression levels of pAkt, pmTOR, and PI3K in SCCs before and after switching to mTOR inhibitors.
Main Methods:
- Immunohistochemical analysis was performed on 23 SCC tissue sections from OTR.
- Antibodies targeting pAkt, pmTOR, and PI3K were used to assess protein expression.
- SCC samples were analyzed both before and after the patients were switched to mTOR inhibitors.
Main Results:
- Phosphorylated mTOR (pmTOR) expression was observed in a similar proportion of SCCs before (8/12) and after (8/11) switching to mTORis.
- Phosphatidylinositol 3-kinase (PI3K) was expressed in most SCCs (21/23), and pAkt was universally expressed in all SCCs.
- No significant changes in the immunohistochemical expression of pmTOR, PI3K, or pAkt were detected after switching to mTORis.
Conclusions:
- mTOR inhibitors do not significantly alter the expression of pmTOR, PI3K, or pAkt in cutaneous SCCs from OTR.
- The study suggests that the upstream components of the mTOR pathway in these skin tumors remain largely unchanged despite mTOR inhibition.
- Further research may be needed to fully elucidate the mechanisms of action of mTORis in preventing skin tumors in OTR.
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