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: Evangelia Papadavid, Massimo Pignatelli, Spyridon Zakynthinos, Thomas Krausz, Anthony C Chu
• Journal: The Journal of pathology (J Pathol) Vol. 196 Issue 2 Pg. 154-62 (Feb 2002) ISSN: 0022-3417 [Print] England
• PMID: 11793366 (Publication Type: Journal Article)
• Copyright: Copyright 2001 John Wiley & Sons, Ltd.

Chemical References

• Biomarkers, Tumor
• CTNNA1 protein, human
• CTNNB1 protein, human
• Cadherins
• Cytoskeletal Proteins
• Desmoplakins
• JUP protein, human
• Ki-67 Antigen
• Trans-Activators
• alpha Catenin
• beta Catenin
• gamma Catenin

Topics

• Adult
• Biomarkers, Tumor (analysis)
• Cadherins (analysis)
• Carcinoma, Squamous Cell (chemistry, pathology)
• Cytoskeletal Proteins (analysis)
• Desmoplakins
• Female
• Humans
• Immunocompromised Host
• Immunohistochemistry (methods)
• Ki-67 Antigen (analysis)
• Male
• Middle Aged
• Precancerous Conditions (metabolism, pathology)
• Skin Neoplasms (chemistry, pathology)
• Trans-Activators
• alpha Catenin
• beta Catenin
• gamma Catenin