title: Abnormal immunoreactivity of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex in premalignant and malignant non-melanocytic skin tumours.
abstract: E-cadherin/catenin (alpha-, beta-, and gamma-) complex plays a critical role in the control of epithelial differentiation. The aim of this study was to examine the immunoreactivity of E-cadherin and alpha-, beta-, and gamma-catenins in premalignant and malignant non-melanocytic skin tumours (NMST) and to correlate their expression with the grade of tumour differentiation, as assessed by the established histopathological criteria and by the Ki-67 index. Benign NMSTs were also studied. To investigate any possible influence of immunosuppression in the expression of E-cadherin and catenins, the study compared tumours obtained from renal transplant recipients (RTRs) and immunocompetent patients. Immunoperoxidase staining of E-cadherin and alpha-, beta-, and gamma-catenins was performed in 42 squamous cell carcinomas (SCCs) (26 from RTRs and 16 from non-RTRs), 30 lesions of Bowen's disease (11 from RTRs and 19 from non-RTRs), 11 atypical squamoproliferative lesions from RTRs, 19 actinic keratoses (9 from RTRs and 10 from non-RTRs), and 20 viral warts from RTRs. The findings of this study were as follows. Firstly, the probability of abnormal expression of E-cadherin and alpha-, beta-, and gamma-catenins increased from benign to premalignant and malignant NMSTs (p<0.001 for all). Secondly, there was agreement in abnormal expression between most of the molecules measured in malignant and premalignant NMSTs (p<0.05). Thirdly, in SCC, abnormal expression of E-cadherin and catenins was more frequent in lesions with a high (>40%) Ki-67 index than in those with a low Ki-67 index (<40%) (p=0.003). However, only the abnormal expression of gamma-catenin increased with the grade of SCC differentiation (p=0.008). Fourthly, abnormal expression of gamma-catenin predicted a high proliferation index (Ki-67 index 40%) in NMSTs (p<0.01, OR=6.19). Finally, there was no difference in the abnormal expression of E-cadherin and catenins between NMSTs from immunosuppressed and immunocompetent patients. Thus, abnormal expression of the E-cadherin/catenin complex was quite common in SCC and Bowen's disease and also in a proportion of intraepithelial dysplastic lesions, such as atypical squamoproliferative lesions and actinic keratosis, suggesting that these changes may be early indicators of the neoplastic process. Abnormal expression of gamma-catenin was the sole predictor of high proliferation in NMST and was also correlated with the tumour grade, suggesting a possible important role for gamma-catenin in tumourigenesis.
authors.affiliation: Imperial College School of Science, Technology and Medicine, Dermatology Unit, Hammersmith Campus, London W12 ONN, UK. epapad@otenet.gr
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papadavid
authors.forename: Massimo
authors.initials: M
authors.lastname: Pignatelli
authors.forename: Spyridon
authors.initials: S
authors.lastname: Zakynthinos
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Chu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis*; D051180:Desmoplakins; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: D014408:Biomarkers, Tumor; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin