Related Experiment Videos
Comparison of mitotic cyclins and cyclin-dependent kinase expression in keratoacanthoma and squamous cell carcinoma
T A Tran1, J S Ross, J R Boehm
1Department of Pathology and Laboratory Medicine, Albany Medical College, New York 12208, USA.
Abstract:
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.
Insights
Keratoacanthoma (KA) and squamous cell carcinoma (SCC) share expression patterns of cell-cycle proteins, suggesting KA is a variant of SCC. Regressing KAs show distinct cyclin expression, influencing their involution tendency.
Area of Science:
- Oncology
- Cell Biology
- Dermatopathology
Background:
- Cell-cycle dysregulation, involving cyclins and cyclin-dependent kinases, is crucial in cancer development.
- Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are skin neoplasms with overlapping features, necessitating differentiation.
- Understanding mitosis-related antigen expression may elucidate KA's unique regression tendency.
Purpose of the Study:
- To compare immunohistochemical expression of mitotic cyclins (A and B) and p34(cdc2) in KAs and SCCs.
- To investigate if these markers correlate with KA's regression.
- To determine if KA is a distinct entity or a variant of SCC.
Main Methods:
- Immunohistochemical analysis of cyclins A, B, and p34(cdc2) in 21 KAs, 8 regressing KAs, and 28 SCCs.
- Evaluation of expression patterns (basal, parabasal, diffuse) and 'hot spot' levels.
- Comparison of marker expression between KA, regressing KA, and SCC groups.
Main Results:
- KAs exhibited predominantly basal/parabasal cyclin A/B expression, unlike SCCs' diffuse pattern (p < 0.01).
- No significant difference in peak cyclin A/B expression levels between KAs and SCCs.
- Regressing KAs showed more regional cyclin labeling but lower mean expression than mature KAs (p < 0.05).
- p34(cdc2) expression showed no significant differences across groups.
Conclusions:
- Mitotic cyclins play a role in the pathogenesis of both SCC and KA.
- Overlapping antigen expression suggests KA is a variant of SCC with a strong tendency for spontaneous regression.
- Cyclin expression differences in regressing KAs may be linked to their involution process.