Premalignant and malignant skin diseases Assessment of proliferation indexes

Abstract

Malignant diseases, such as proliferative skin lesions are characterized by inappropriate cell increase. Activation of proto-oncogenes and inactivation of tumour suppressor genes are the harmful genetic events that are responsible for malignant transformation (1). Carcinogenesis in the skin is a complicated process characterized by the appearance of cells which have escaped from the normal growth control mechanisms, following in an increase of proliferative activity in the cells (2). The prevalent risk factors for skin cancer are exposure to ultraviolet (UV) radiation and fair skin that is receptive to sunburn. Increasing frequency of exposure, immune status, age, male gender and DNA repair disorders such as xeroderma pigmentosum also assist to increased risk (3). The association between UV exposure and cancer is powerful for SCC but less well-defined for BCC, as nearly one third of all BCC originates in anatomical sites receiving minimal UV exposure. Skin temperature may also be a risk factor. Cultured immortalized human kératinocytes have been shown to spontaneously transform to a tumorigenic phenotype when incubated at elevated temperature (4). Some investigations indicate that human papilloma virus infection may be a risk factor for skin cancer, though the relationship is not clear (5). Solid-organ transplant recipients are at extremely high risk for SCC (6). The long-term immunosuppressive therapy is probably the cause of the increased frequency of SCC in these patients, particularly in persons with chronic actinic damage (7).The mechanism of UV-induced photo carcinogenesis appears to implicate the inactivation of the p53 tumour suppressor gene (8). Several studies have reported that p53 distortions play a critical role in the development and progression of various human malignancies. The p53 gene is involved in the regulation of cell cycle control and apoptosis'. Mutations in this gene could presumably cancel p53 function, allowing accumulation of mutant cells due to loss of the UV-induced apoptosis of DNA-damaged cells (9). This leads to clonal expansion of p53-mutated kératinocytes, which could eventually acquire the second mutation that leads to the progression to multiple mutations. They can be accumulated. Therefore, this clonal expansion is regarded as a key initiating step in epidermal carcinogenesis (10). Precancerous dermatoses occur prior to development of epidermal malignancies (6). Because skin lesions are visible and easily accessible, skin cancer provides us with an excellent model for studying the development and growth of cancer in humans. Furthermore, the carcinogenic agents to the skin are well known. This is of special interest so far as UV radiation is the most important carcinogen and puts a specific signature on the DNA (10).Actinic keratosis (AK), also known as senile or solar keratosis is the most common precancerous dermatosis and is attributable to UV radiation (11). This UV-induced lesion is usually seen as multiple lesions in sun-exposed skin in elderly persons. This sunrelated d...