Jørgen Lock-Andersen

Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combined advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantified 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and novel proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research ( www.skin.science ).

Sentinel node biopsy (SNB) is used in patients with cutaneous malignant melanoma (MM) to detect subclinical spread to the regional lymph nodes, after which a radical lymph node dissection can be performed. Since 2001, the Department of Plastic Surgery, Roskilde Amts Sygehus, has used SNB routinely in patients with cutaneous MM who have a statistical risk of at least 10% of harbouring subclinical lymph node metastasis. In the four-year period from 2001 to 2004, 248 consecutive patients with primary MM underwent SNB at the time of radical surgery for their MM. If metastatic spread was found in the removed sentinel node, a radical lymph node dissection was performed shortly afterward. All patients were followed up after their operation in the department's outpatient clinic. Regional lymph node metastatic spread was found by SNB in 32% of the patients. At radical lymph node dissection, further metastatic lymph nodes were found in 24% of the dissected cases. The median follow-up time was 21 months (range 1-51 months). 7% of SN-negative cases developed recurrence during follow-up, in contrast to 23% of the SN-positive cases. The median time to recurrence was 14 months. The two-year and four-year disease-free survival rates were 93% and 85% in the SN-negative group and 73% and 55% in the SN-positive group, respectively. Risk factors for recurrence were: extracapsular SN growth, more than one metastatic SN and further lymph node metastases being found by formal node dissection. 18% of the SN-positive patients died during the follow-up period, in contrast to 3% of the SN-negative cases. The MM-specific two-year and four-year survival rates were 84% and 64% in the SN-positive group and 99% and 97% in the SN-negative group, respectively. Sentinel node biopsy is a procedure that detects MM patients who have a very high risk of recurrence and death by MM within a few years after primary treatment. SNB status is a very strong prognostic factor, and SN-positive cases should be followed carefully.

Status of the regional lymph nodes is a strong prognostic factor in patients with cutaneous malignant melanoma (CMM) and can be assessed by sentinel lymph node biopsy (SLNB). We present our technique of preoperative lymphatic mapping and intraoperative vital dye and handheld gamma probe. Our results and three years follow-up of its routine use in 198 patients with verified primary CMM are presented. Median follow-up time was 24 months (range 1-47). Metastatic regional lymph node disease was found by SLNB in 61 patients (31%) and additional metastatic nodes were found by formal node dissection in 30% of these cases. Complications were relatively mild but included one case of lymphoedema in a node negative patient. By follow-up, 13% had developed a recurrence including 26% of node positive patients and 8% of node negative patients. Mortality was also substantially higher in node positive cases with 18% dying in the follow-up period and 3% in the node negative group. The SLNB procedure was associated with a false negative rate of 8%. Using the presented technique, we found that SLNB was a useful procedure for staging patients with CMM and for selecting patients for more extensive metastatic screening and inclusion in trials of adjuvant treatments.

To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as ri...

In two identical and simultaneously performed case–control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients and 174 matched controls and in 168 CMM patients and 176 matched controls. Measurements were performed at the forehead, the upper chest, the upper back, the lateral and medial aspects of the upper arm, and the buttocks. Self-estimation of sun exposure in childhood, in youth and in adulthood was performed by all subjects. There were no statistically significant differences in constitutive skin pigmentation at the buttocks between BCC patients and controls (P = 0.96) or between CMM patients and controls (P = 0.13). Facultative skin pigmentation in ultraviolet-exposed sites was not significantly different between BCC patients and controls except that women patients had higher pigmentation at the lateral side of the upper arm. For CMM, men patients had higher pigmentation at the lateral side of the upper arm. Self-estimations of sun exposure did not show differences between patients and controls but indicated high exposure levels in childhood and youth and in adult leisure time. Sun exposure estimated by increase in facultative pigmentation above the constitutive level (the Sun Exposure Index) was not significantly different between BCC patients and controls, whereas CMM men patients had higher estimates for the lateral side of the upper arm, the chest and the back.

To investigate age and gender trends in facultative and constitutive skin pigmentation we measured skin pigmentation non-invasively and objectively by skin reflectance spectroscopy in 653 caucasians (336 females and 317 males; mean age 38 years, range 0–85) who were not using artificial tanning devices. In all subjects, measurements were performed in the late winter and pre-spring period at five sites exposed to ultraviolet (UV) radiation: the forehead, the upper chest, the upper back and the lateral and medial aspects of the upper arm, and in UV-unexposed buttock skin. Constitutive pigmentation at the buttocks was highest in the first years of life and then decreased substantially during the first two decades of life (P < 0.01). After the age of 25 years, buttock pigmentation remained at a constant level (P = 0.20). There was no gender difference in constitutive pigmentation. Facultative skin pigmentation increased with age for all the measured sites with the highest levels found at the lateral aspect of the upper arm. Based on observations in this study we propose the idea of a ‘sun exposure index’ (SEI) for individuals, based on objective measurements of skin pigmentation. The SEI is calculated as the increase in facultative pigmentation above the constitutive level and is expressed as a percentage of the constitutive level. The SEI appeared to be related to cumulative lifetime UV exposure and may be used in epidemiological research as an objective estimate of UV exposure at different body sites in caucasians.

A total of 805 sunbathing Caucasians were interviewed about sunprotection behaviour and self-assessed burning tendency. Sixty-seven percent of the interviewed sunbathers used one or more sunscreen factors. Sunscreen-users and nonusers were exposed to the sun 206 min and 197 min (P = 0.186), respectively. The sunscreen users were exposed to a marginally higher UV dose than non-sunscreen users, 4.8 SED versus 4.5 SED (P = 0.0348). The rate of sunscreen users was significantly higher among subjects who stated that they always were sunburnt in the spring when not using a sunscreen than subjects who stated that they never were sunburnt in the spring when not using a sunscreen (P = 0.0001). However, when comparing subjects that always burn in the spring and subjects that never burn in the spring, we found no significant difference between level of the sun-protection factor (P = 0.11) nor the duration of sun exposure (P = 0.967), nor to which UV doses the subjects were exposed (P = 0,562). Furthermore we found that the interviewed sunbathers interpreted to "be sunburnt" as more severe than "to turn red". Public campaigns recommend the use of sun protection cream when sunbathing without using other sun protective strategies; however, the use of sun protection cream is inadequate among sunbathers. More education is required to persuade those with more sun-sensitive skin to use a higher protection-factor, to reduce sun exposure at times when UV radiation is most intense, and to reduce the duration of exposure.