. The expression of the cell-cell adhesion molecules E-and P-cadherin has been analyzed in seven mouse epidermal keratinocyte cell lines representative of different stages of epidermal carcinogenesis . An inverse correlation between the amount of E-cadherin protein and tumorigenicity of the cell lines has been found, together with a complete absence of E-cadherin protein and mRNA expression in three carcinoma cell lines (the epithelioid HaCa4 and the fibroblastoid CarB and CarC cells) . A similar result has been detected in tumors induced in nude mice by the cell lines, where induction of E-cadherin expression takes place in moderately differentiated squamous cell carcinomas induced by HaCa4 cells, although at much lower levels than in well-differentiated tumors induced by the epithelial PDV or PDVC57 cell lines. Complete absence of E-cadherin expression has been C ELL adhesion mechanisms play a major role in vital processes such as embryogenesis, tissue and organ pattern formation and maintenance of specific tissue architecture (Edelman, 1985 ;Thiery et al., 1982) . Calciumdependent cell-cell adhesion molecules are one ofthe major components involved in the various processes of intercellular adhesion . In vertebrates, calciumdependent cell-cell adhesion molecules identified so far constitute a family of transmembrane glycoproteins, of 119-135 kD, for which the general term cadherins has been proposed (see Takeichi, 1988Takeichi, , 1990 .The different members of the family, identified in various tissues and species, can be grouped in three distinct categories, exemplified in the mouse by (a) N-cadherin (Hatta and Takeichi, 1986;Hatta et al., 1985), present mostly in neural tissues ; (b) E-cadherin (identical to uvomorulin) (YoshidaNoro et al., 1984;Hyafil et al., 1980;Peyrieras et al., 1985), expressed in epithelial tissues ; and (c) P-cadherin, present both in epithelial and nonepithelial tissues with major prevalence at the placenta (Nose and Takeichi, 1986) . All members of the family present strong homology at the amino acid © The Rockefeller University Press, 0021-9525/91/10/517/17 $2 .00 The Journal of Cell Biology, Volume 115, Number 2, October 1991517-533 observed in spindle cell carcinomas induced by CarB or CarC cells. P-cadherin protein was detected in all cell lines that exhibit an epithelial (MCA3D, AT5, PDV, and PDVC57) or epithelioid (HaCa4) morphology, as well as in nude mouse tumors, independent of their tumorigenic capabilities. However, complete absence of P-cadherin was observed in the fibroblast-like cells (CarB and CarC) and in spindle cell carcinomas. The introduction of an exogenous E-cadherin cDNA into HaCa4 cells, or reactivation of the endogenous E-cadherin gene, leads to a partial suppression of the tumorigenicity of this highly malignant cell line . These results suggest a role for E-cadherin in the progression to malignancy of mouse epidermal carcinogenesis . They also suggest that the loss of both E-and P-cadherin could be associated to the final stage of carcinogenesis, ...

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Summary E-cadherin (E-CD) is a calcium-dependent cell-cell adhesion molecule which is expressed in almost all epithelial tissues. E-CD expression is involved in epidermal morphogenesis and is reduced during tumour progression of mouse epidermal carcinogenesis. It has been suggested that E-CD could play a role as an invasion-suppressor molecule. In the present work we have studied the E-CD expression in 31 patients with basal cell carcinoma (BCC) using an immunohistochemical technique with a monoclonal antibody (HECD-1) specific for human E-CD. E-CD expression was preserved in all specimens of superficial and nodular BCC, and was reduced in 10 of 15 infiltrative BCCs. A heterogeneous distribution of cells with different immunostaining intensity was more frequently observed in specimens of infiltrative BCC. These results suggest that E-CD might be related to the growth pattern and the local aggressive behaviour of BCC, and support the idea that E-CD might play a role as an invasion-suppressor molecule in vivo.

This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.