| Non-melanoma skin cancers are the most common malignancies in the western world and their incidences are rising. Because they are so common and easily accessible, they offer a unique opportunity to study the process of carcinogenesis in human. In particular neoplasms with a squamous phenotype can be very informative because they manifest themselves clinically in a range from benign forms (keratoacanthoma), squamous premalignant tumours (actinic keratosis (AK), carcinoma in situ (Bowen's disease, BD)) and the malignant squamous cell carcinomas (SCC). Recently, the term keratinocytic intraepidermal neoplasia (KIN), a classification for squamous premalignancies, has been introduced. It is of increasing clinical importance to get a better understanding of the carcinogenesis of these cutaneous squamous premalignancies in order to be able to design mechanistically based intervention strategies and it is of scientific relevance to study the development from paralesional skin of squamous premalignancies, to KIN I, KIN II, and KIN III in order to get a better understanding of the process of carcinogenesis. New therapeutic and diagnostic tools in squamous premalignancies of the skin may be found using fluorescence diagnosis (FD) and photodynamic therapy (PDT). PDT with topical 5-aminolaevulinic acid (5-ALA) which leads to an accumulation of the photosensitive protoporphyrin IX (PpIX), has proven to cure squamous premalignancies. PDT may also be of relevance for non-malignant skin disorders, characterized by epidermal proliferation. It has been shown that PDT with topical 5-ALA improves psoriasis, a very common skin disease with a prevalence of 2-3%. The methodology has not yet been standardized and so far inconsistent clinical responses have, however, limited the development of this treatment approach for psoriasis till now. This new treatment modality in the field of phototherapy may well be a non-carcinogenic alternative for the PUVA and UVB phototherapy, which are standard treatments in psoriasis at this moment. In patients with multiple skin (pre)malignancies a diagnostic problem, as well as a therapeutic question has become evident. For these patients, who have to undergo many diagnostic biopsies and surgical procedures every year, alternative non-invasive diagnosis and treatment modalities would be very welcome. FD with 5-ALA and Woods light may be a new alternative approach. Aims: - to identify, quantify and characterise target cell populations for FD and PDT in psoriasis and squamous premalignancies of the skin; - to investigate the centre and the marginal zone of squamous premalignancies of the skin as visualised with or without fluorescence by assessment of the KIN classification, flow cytometric DNA content analysis and the expression of Ki-67 and p53; - to demonstrate a correlation between the expression of Ki-67 and p53, the grade of KIN and the flow cytometric DNA content analysis in squamous premalignancies of the skin; - to evaluate the value of fluorescence-guided biopsies in patients with multiple cutaneous squamous premalignancies; - to correlate fluorescence with benign hyperproliferation, the centre and margin of active psoriatic plaques will be investigated with FD and in biopsies correlation with Ki-67 and p53 will be studied. |
