Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

The time course of the development of distant metastasis was more or less the same irrespective of the metastatic pathway; this suggests that in patients with in-transit or satellite metastasis or regional lymph node metastasis, haematogenic metastatic spread had already taken place. Thus, the diagnostic value of sentinel lymph node biopsy and the therapeutic benefit of elective lymph node dissection may be limited, as satellite and in-transit metastases or direct distant metastases will not be detected and haematogenous spread may already have taken place when the intervention is performed.

The results of our study suggest that an elaborated follow-up schedule in cutaneous melanoma is suitable for the early detection of second primary melanomas and early recurrences. The intensity of clinical and technical examinations can be reduced during follow-up of patients in the primary tumor stages and may be intensified in locoregional disease. Recommendations for an effective follow-up strategy are outlined.

The clinical classification of squamous cell carcinoma, which was established primarily by the International Union Against Cancer (UICC), does not permit optimal estimation of expected metastasis. The authors' results indicate that metastasis can be more accurately estimated on the basis of invasion depth, histopathologic grading, and especially tumor thickness. One essential advantage of these criteria is that they can be established by a histopathologist. It is interesting to note that in the authors' collective no carcinoma less than 2 mm thick metastasized, that is, a relatively high percentage of carcinomas (48%) can be graded as no-risk carcinomas. The risk of metastasis for undifferentiated carcinomas greater than 6 mm thick that have infiltrated the musculature, the perichondrium, or the periosteum, however, is quite high. Tumors between 2 and 6 mm thick with moderate differentiation and a depth of invasion that does not extend beyond the subcutis can be classified as low-risk carcinomas.

Background. Anatomic location has been identified by several investigators as a significant prognostic factor for patients with primary cutaneous melanoma (CM). However, the best determination of higher and lower risk sites is still controversial, and the biologic significance of tumor site in the course of primary CM is unknown. The aim of the present study was to identify higher and lower risk sites based on multivariate analysis. Methods. A series of 5093 patients with invasive primary cutaneous melanoma followed from 1970 to 1988 at four university centers in Germany was investigated using the multivariate Cox proportional hazard model to analyze the importance of anatomic location for survival probability. Results. The anatomic location was found to be a highly significant prognostic factor for patients with primary melanoma by multivariate analysis (P < 0.0001). An optimized classification into sites of higher and lower risk with respect to survival was evaluated by multivariate analysis controlling for the possible confounding effects of the other significant prognostic factors. Relative to the lower leg as the prognostically favorable baseline, the following locations were associated with a significantly higher risk of death caused by primary cutaneous melanoma: back and breast (thorax), upper arm, neck, and scalp (TANS regions). The lower trunk, thigh, lower leg, foot, lower arms, hands, and face were identified as lower risk sites. Conclusions. Anatomic location was confirmed as an independent prognostic factor for patients with primary cutaneous melanoma. The TANS regions were identified as high risk sites, and the lower trunk, thigh, lower leg, foot, lower arms, hands, and face were identified as intermediate sites.