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 carcinogene sis. In order to determine whether keratoacanthoma (KA) is unique or a vari ant of squamous cell carcinoma (SCC) and whether expression of mitosis-rela ted antigens are associated with KAs' tendency to regress, we compared the immunohistochemical expression of mitotic cyclins (cyclins A and B) and the ir cyclin-dependent kinase p34(cdc2) in 21 KAs, 8 regressing KAs, and 28 co nventional squamous cell carcinomas. KAs showed both overlap and significan t differences in expression of these mitosis-related antigens compared to S CCs. Basal and parabasal pattern of expression of cyclins A and B significa ntly predominated in KAs in contrast to SCCs which exhibited diffuse patter n (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, distribu tion or mean levels of expression were found. For cyclins A and B, regressi ng 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 ex pression for these mitosis-related antigens suggest that KAs represent a va riant of SCC that exhibit an overwhelming but not absolute tendency to invo lute.