Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas.
BACKGROUND
Immunosuppression favors the development of skin cancer. Experimental data suggest that sirolimus (SRL) has antitumoral and antiangiogenic properties. An investigation was undertaken into the effects of SRL on squamous cell carcinoma (SCC) developing in organ transplant recipients (OTR) receiving immunosuppressive treatments, with special emphasis on vascularization.


METHODS
SCC that developed in eight OTR before and after conversion from calcineurin inhibitors (CNI) to SRL were compared for thickness, differentiation, ulceration, perineural invasion, density of peritumoral infiltrate, peritumoral vascularization, density of T-regulatory cells and of intratumoral Langerhans cells and growth fraction.


RESULTS
SCC developing under SRL showed lower peritumoral vascularization and thickness, and higher growth fraction and density of peritumoral T-regulatory cells.


CONCLUSIONS
Conversion from CNI to SRL at clinically relevant doses is associated in vivo with a reduced vascularization and thickness of post-transplant human cutaneous SCC. This effect could account for the beneficial effect of SRL on immunosuppression-induced skin carcinogenesis in humans.
Rival-Tringali
Anne-Laure
AL
Hospices Civils de Lyon, Hôspital Edouard Herriot, Clinique Dermatologique (Pav. R), 69437 Lyon Cedex 03, France.
Euvrard
Sylvie
S
Decullier
Evelyne
E
Claudy
Alain
A
Faure
Michel
M
Kanitakis
Jean
J
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D065095:Calcineurin Inhibitors; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000209:etiology / Q000473:pathology; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D016027:Heart Transplantation; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011183:Postoperative Complications; D020123:Sirolimus / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000098:blood supply* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus