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Der „Basalzellenkrebs“
E. Krompecher, 1903
1894
Illustration P.G. Unna Today
Photography W. Neuse
1895
Illustration G. Thibierge
Today
Photography W. Neuse
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
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 !
BASAL CELL CARCINOMA
AND IONIZING RADIATION
Multiple BCCs 20 yrs after irradiation of Hodgkin´s disease
BASAL CELL CARCINOMA
DISTRIBUTION
Head/Neck 60 %
Nose 14 %
Trunk 30 %
Extremities 10 %
BASAL CELL CARCINOMA
PATHOGENESIS
BCC
Genetic
Predisposition Skin type
DNA
Repair
Immuno-
Suppression
UV
Mutations
Autosomal dominant
Multiple BCCs at young age
Skin, CNS, Skeletal involvement
Predisposition to malignancy
(medulloblastoma)
PTCH germ line mutations
NEVOID BASAL CELL CARCINOMA-
SYNDROME (NBCCS)
Ptch Smoh
Shh
extracellular
intracellular
Gli1/2
Nucleus
HIP
PTCH Gli1/2
Sufuh
THE SONIC HEDGEHOG PATHWAY
CCNB1/D2
FOXM1/FOXE
BCL2
PTCH
Human homolog of the Drosophila - Gene patched
Drosophila: segmental development
Function: Receptor for the hedgehog protein Tumor suppressor
PTCH Mutant Wild type
ANALYSIS OF SHH PATHWAY GENES
IN SPORADIC 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
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
PTCH+/- MOUSE MODEL
Model of human NBCCS
Body size increased
Medulloblastomas (15%)
BCCs after repetitive
UVB exposure
Medulloblastoma
UVB induced BCCs
„MOUSE SOLARIUM“
GDC-0449
SMALL MOLECULE SMO-INHIBITOR
von Hoff et al., N Engl J Med 2009
PHOTODYNAMIC THERAPY (PDT)
Topical application of
ALA 20 % (3 - 5 h) PDT with
red light
634 nm
PDD with
Wood-Light
417 nm
PHOTODYNAMIC THERAPY
OF NBCCS
Before therapy After 4x PDT
FLUORESCENCE DIAGNOSIS
Pre-operative determination of tumor margins
And I told him, put some cream on
UV PROTECTION