OBC | New development in the therapy of basal cell carcinoma
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Thomas Ruzicka, LM University of Munich, Germany New development in the therapy of basal cell carcinoma http://obc2012.outofthebox.si/
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OBC | New development in the therapy of basal cell carcinoma
- 2. 1894 Today Illustration P.G. Unna Photography W. Neuse
- 3. 1895 Today Illustration G. Thibierge Photography W. Neuse
- 4. BASAL CELL CARCINOMA INCIDENCE Australia up to 2 % per year USA White population 407 / 100 000 / year 1 million cases in 2005 Half of all cancers 80 % of all NMSC Worldwide Increasing incidence
- 5. BASAL CELL CARCINOMA RISK FACTORS Skin type I – II Ionising radiation Burns As, Tar, Smoking Immunosuppression Age > 60 Previous BCC: RR 10x Gene mutations Ultraviolet !
- 8. BASAL CELL CARCINOMA AND IONIZING RADIATION Multiple BCCs 20 yrs after irradiation of Hodgkin´s disease
- 9. BASAL CELL CARCINOMA DISTRIBUTION Head/Neck 60 % Nose 14 % Trunk 30 % Extremities 10 %
- 14. BASAL CELL CARCINOMA PATHOGENESIS UV Immuno- DNA Suppression Mutations Repair BCC Genetic Skin type Predisposition
- 15. NEVOID BASAL CELL CARCINOMA- SYNDROME (NBCCS) Autosomal dominant Multiple BCCs at young age Skin, CNS, Skeletal involvement Predisposition to malignancy (medulloblastoma) PTCH germ line mutations
- 16. THE SONIC HEDGEHOG PATHWAY Shh extracellular Ptch Smoh intracellular PTCH Gli1/2 HIP Sufuh CCNB1/D2 Gli1/2 FOXM1/FOXE Nucleus BCL2
- 17. PTCH Human homolog of the Drosophila - Gene patched Wild type PTCH Mutant Drosophila: segmental development Function: Receptor for the hedgehog protein Tumor suppressor
- 18. ANALYSIS OF SHH PATHWAY GENES IN SPORADIC BCCs PTCH mutations: 28/42 (67%) SMOH mutations: 4/42 (10%) SUFUH mutations: 2/42 (22%) GLI1/GLI2 overexpression: 42/42 (100%) In 70% of BCCs somatic mutations of Shh genes Shh pathway is constitutively activated in all BCCs Wolter et al., Cancer Res 57: 2581-2585, 1997 Reifenberger et al., Cancer Res 58: 1798-1803,1998 Reifenberger et al., Br J Dermatol: 43-51, 2005
- 19. PTCH+/- MOUSE MODEL Model of human NBCCS Body size increased Medulloblastomas (15%) Medulloblastoma BCCs after repetitive UVB exposure UVB induced BCCs
- 20. „MOUSE SOLARIUM“
- 23. von Hoff et al., N Engl J Med 2009
- 27. PHOTODYNAMIC THERAPY (PDT) PDD with Wood-Light Topical application of 417 nm PDT with ALA 20 % (3 - 5 h) red light 634 nm
- 28. PHOTODYNAMIC THERAPY OF NBCCS Before therapy After 4x PDT
- 29. FLUORESCENCE DIAGNOSIS Pre-operative determination of tumor margins
- 31. And I told him, put some cream on
- 32. UV PROTECTION