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.


OBJECTIVE
To determine the pattern of E-cadherin and alpha-, beta- and gamma-catenin immunostaining in keratoacanthoma (KA) and to evaluate its potential value in routine histopathology in differentiating KA with benign from that with malignant biological behaviour.


METHODS
We examined the expression of E-cadherin and alpha-, beta- and gamma-catenin in KA and correlated the histopathological features with the immunohistochemical findings. Next, we compared the immunohistochemical findings of KA with those found in malignant (squamous cell carcinoma, SCC) and benign (warts) lesions. In addition to the established histopathological criteria we used the Ki-67 index, a well-known marker of cell proliferation. Immunoperoxidase 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 the 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 immunostaining and a low Ki-67 index. The remaining 'classical' KAs showed abnormal expression, in a staining pattern resembling that of well-differentiated SCC. All 'borderline' KAs showed a high Ki-67 index (> 40%) and abnormal expression of the adhesion molecules studied, identical to that of poorly differentiated SCC. Expression of E-cadherin and alpha-, beta- and gamma-catenin was found to be more frequently abnormal in 'borderline' KA compared with that in 'classical' KA (P < 0.05). Among E-cadherin and alpha-, beta- and gamma-catenin expression and Ki-67 index, only the expression of beta-catenin 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 in 'classical' KA (P < 0.05). In total, as well as in 'classical' or 'borderline' 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 that found in normal epidermis, overlapping with well-differentiated SCC in some cases. In 'borderline' KA, expression of adhesion molecules is identical to that in poorly differentiated SCC.
Papadavid
E
E
Dermatology Unit, Imperial College of Science, Technology and Medicine, Hammersmith Campus, London W12 0NN, UK. epapad@otenet.gr
Pignatelli
M
M
Zakynthinos
S
S
Krausz
T
T
Chu
A C
AC
D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D003937:Diagnosis, Differential; D006801:Humans; D007124:Immunoenzyme Techniques; D007636:Keratoacanthoma / Q000175:diagnosis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism; D015534:Trans-Activators; D014860:Warts / Q000175:diagnosis / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
D015415:Biomarkers; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin