Comparison of mitotic cyclins and cyclin-dependent kinase expression in keratoacanthoma and squamous cell carcinoma

Disruption of the cell-cycle regulation through over-expression or mutation of cyclins and cyclin-dependent kinases has been implicated in carcinogenesis. In order to determine whether keratoacanthoma (KA) is unique or a variant of squamous cell carcinoma (SCC) and whether expression of mitosis-related antigens are associated with KAs' tendency to regress, we compared the immunohistochemical expression of mitotic cyclins (cyclins A and B) and their cyclin-dependent kinase p34(cdc2) in 21 KAs, 8 regressing KAs, and 28 conventional squamous cell carcinomas. KAs showed both overlap and significant differences in expression of these mitosis-related antigens compared to SCCs. Basal and parabasal pattern of expression of cyclins A and B significantly predominated in KAs in contrast to SCCs which exhibited diffuse pattern (cyclin A 86%/cyclin B 64% vs. 25%/36%, p < 0.01). However, no differences in the highest mean level of expression in 'hot spot' loci of cyclins A and B were identified comparing KAs to SCCs (19%/12% vs. 25%/13%, p > 0.05). For the cyclin-dependent kinase p34(cdc2), no differences in pattern, distribution or mean levels of expression were found. For cyclins A and B, regressing KA showed significantly more regional tumor labeling (88%/88% vs. 57%/33%, p = 0.03) and a lower mean level of immunoreactivity (5%/4% vs. 19%/12%, p = 0.001) compared to mature KAs. These findings indicate a role for mitotic cyclins in the evolution of both SCC and KA. The overlapping patterns of expression for these mitosis-related antigens suggest that KAs represent a variant of SCC that exhibit an overwhelming but not absolute tendency to involute.