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 !
6.
7.
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 %
10.
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12.
13.
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