bromochloroacetic-acid and Remission--Spontaneous

Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers. Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear staining was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis.

Topics: Animals; Carcinoma, Squamous Cell; Cell Nucleus; Coloring Agents; Disease Progression; Fixatives; Formaldehyde; Genes, p53; Half-Life; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Keratoacanthoma; Mutation; Neoplasm Regression, Spontaneous; Rabbits; Remission, Spontaneous; Skin; Skin Neoplasms; Sunlight; Tumor Suppressor Protein p53

Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The T lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin-2 receptor (IL-2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM-1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL-2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response.

Topics: Aged; Aged, 80 and over; Antigens, CD; Carcinoma, Squamous Cell; CD3 Complex; CD36 Antigens; CD4 Antigens; Epidermis; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratins; Keratoacanthoma; Lymphocyte Activation; Middle Aged; Platelet Membrane Glycoproteins; Receptors, Interleukin-2; Remission, Spontaneous; Skin Diseases; Skin Neoplasms; T-Lymphocytes