The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelialmesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.

Hereditary palmoplantar keratoderma is characterized by hyperkeratosis of the skin of palms and soles. An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, frequently complicated by fungal infections, is encountered in northern Sweden with a prevalence of 0.3-0.55%. We have examined two families with this type of palmoplantar keratoderma and localized the causative genetic defect to a 14 cM interval on chromosome 12q11-q13, a region known to contain the keratin type II gene cluster as well as the retinoic acid receptor gamma gene. The palmoplantar keratoderma variant investigated in this study is thus genetically different from epidermolytic palmoplantar keratoderma, which recently has been shown to result from mutations in the gene for the type I keratin 9.

To assess whether the increase in malignant melanoma incidence could be due, at least in part, to changes in histological criteria of malignancy, pathologists in Australia, France, Italy, New Zealand, Norway, Sweden, the United Kingdom, the United States and the USSR reviewed diagnoses of 50 consecutive pigmented naevi (40 junctional and compound; 10 intradermal) and 20 consecutive malignant melanomas made in each participating centre around 1930, around 1955 and around 1980. Collaborating pathologists re-read the material, 2,665 cases in all, either from the original slide (82%) or from a recut block (17%), gave their diagnosis and indicated whether the lesion was benign (B), dubious benign (DB), dubious malignant (DM) or malignant (M). As the distribution of review diagnoses was much the same whether the original slide or one made from a recut block was read, the material was pooled. Overall, 2.8% of cases originally reported as B/DB were reviewed as DM/M, while 4.4% of the DM/M diagnoses were held to be B/DB. The shifts between categories were greatest around 1955 and least around 1980, suggesting increasing uniformity of interpretation. All available blocks were recut and sections sent to IARC for review: 1.7% (22) of 1293 B/DB diagnoses were considered to be DM/M and 3.3% (18) of 551 DM/M diagnoses were considered to have been B/DB. The consistently low frequency of shift in diagnostic category, whether the material was reviewed in the collaborating laboratories or by one pathologist at IARC, in a study designed to give maximum attention to those lesions--the junctional and compound naevi--in which a change in opinion as to malignancy would be most likely to arise, suggests that pathologists, irrespective of geographical location, are using common criteria. These findings argue against changes in histological interpretation as being responsible for more than a small portion of the continuous increase of some 3% to 8% per annum observed in malignant melanoma incidence. Other explanations, such as an increase in the frequency or potential for malignant transformation of precursor lesions, must be sought. The anatomical distribution of the malignant melanomas examined followed the usual site pattern by sex, and their thickness was observed to decrease over the period of the study in most centres.

Urbach‐Wiethe disease (UWD) is mainly characterized by grossly visible lesions in the skin mouth, pharynx and larynx, consisting of deposits, histopathologically in some respects resembling amyloidotic tissue lesions. UWD was diagnosed in 27 patients belonging to 14 families (16 sibships) in northern Sweden. The findings in the present study are consistent with the hypothesis that the disease is inherited in an autosomal recessive manner. Carriers seem to be diffusely spread along the coast of northern Sweden. Possible effects (micro‐manifestations) of the UWD gene were found among some carriers of the gene.

This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.