Differential expression of p-mTOR in cutaneous basal and squamous cell carcinomas likely explains their different response to mTOR inhibitors in organ-transplant recipients.

BACKGROUND: Mammalian Target of Rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have been shown to reduce cutaneous carcinogenesis in organ-transplant recipients requiring for immunosuppressive treatment to prevent from allograft rejection. Clinical observations suggest that cutaneous squamous cell carcinomas (SCC) are more sensitive than basal cell carcinomas (BCC) to the antitumoral effect of these inhibitors. AIM: To investigate if the different response of SCC and BCC to mTOR inhibitors can be explained by differential expression of molecules involved in the mTOR signaling pathway.
MATERIALS AND METHODS: The expression of phospho-mTOR was immunohistocemically studied in specimens of cutaneous SCC and BCC. Results. All 15 SCCs expressed significant cytoplasmic phospho-mTOR immunoreactivity; by contrast, 12/13 BCC were completely negative, only one BCC exhibited weak phospho-mTOR immunoreactivity.
CONCLUSION: The considerably higher expression of phospho-mTOR in SCC compared to BCC is a likely explanation for their higher sensitivity to mTOR inhibitors.