The potential role of abnormal E-cadherin and alpha-, beta- and gamma-catenin immunoreactivity in the determination of the biological behaviour of keratoacanthoma

Background Failure of E-cadherin and its associated proteins alpha-, beta- and gamma -catenin is believed to lead to disruption of cell-cell adhesion and to contribute to neoplasia. Objectives To determine the pattern of E-cadherin and alpha-, beta- and gam ma -catenin immunostaining in keratoacanthoma (KA) and to evaluate its pote ntial value in routine histopathology in differentiating KA with benign fro m that with malignant biological behaviour. Methods We examined the expression of E-cadherin and alpha-, beta- and gamm a -catenin in KA and correlated the histopathological features with the imm unohistochemical findings. Next, we compared the immunohistochemical findin gs of KA with those found in malignant (squamous cell carcinoma. SCC) and b enign (warts) lesions. In addition to the established histopathological cri teria we used the Ki-67 index, a well-known marker of cell proliferation. I mmunoperoxidase staining of E-cadherin and alpha-, beta- and gamma -catenin , and Ki-67 determination, were performed in paraffin-embedded sections of 12 KAs taken from archival material. On reviewing the histology, seven of t he 12 KAs were characterized as 'classical' KA, and the rest as 'borderline ' KA or KA resembling SCC. Additionally, 28 well, nine moderately and five poorly differentiated SCCs and 20 warts were examined. Results Most 'classical' KAs (79-86%) showed normal membranous immunostaini ng and a low Ki-67 index. The remaining 'classical' KAs showed abnormal exp ression, in a staining pattern resembling that of well-differentiated SCC. All 'borderline' KAs showed a high Ki-67 index (> 40%) and abnormal express ion of the adhesion molecules studied, identical to that of poorly differen tiated SCC. Expression of E-cadherin and alpha-, beta- and gamma -catenin w as found to be more frequently abnormal in 'borderline' KA compared with th at in 'classical' KA (P < 0.05). Among E-cadherin and <alpha>-, beta- and g amma -catenin expression and Ki-67 index, only the expression of beta -cate nin was more frequently found to be abnormal in total SCC than in total KA (P < 0.05). Expression of E-cadherin and <alpha>-, beta- and gamma -catenin was more frequently found to be abnormal in well-differentiated SCC than i n 'classical' KA (P < 0.05). In total, as well as in 'classical' or 'border line' KA, an agreement between expression of E-cadherin and of catenins was seen. Conclusions These findings suggest that E-cadherin and catenins may be very helpful in distinguishing between 'classical' and 'borderline' KA, as the expression of these adhesion molecules in 'classical' KA is identical to th at found in normal epidermis, overlapping with well-differentiated SCC in s ome cases. In 'borderline' KA, expression of adhesion molecules is identica l to that in poorly differentiated SCC.