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