A comparison of expressions of MMP-3, MMP-7, TIMP-1 and apoptosis in keratoacanthoma and squamous cell carcinoma

Background: Keratoacanthoma (KA) is a unique neoplasm, usually accompanied by rapid growth and regression, and the histologic findings resemble those of squamous cell carcinoma (SCC). Histologic differentiation of KA and SCC is challenging, therefore a number of studies have been carried out to differentiate these two entities using immunohistochemical staining. However, the results were inconsistent. There is now a debate as to whether KA is a benign tumor or a less aggressive variant of SCC. Objective: The purpose of this study was to examine the expression patterns of MMP-3, MMP-7, TlMP-1, the apoptotic index in KA and SCC, and the usefulness of immunohistochemical staining in differentiating these two entities. Methods: Formalin-fixed, paraffin-embedded biopsy specimens obtained from 12 KA and 16 SCC patients were investigated for the expressions of MMP-3, MMP-7 and TIMP-1 using an immnohistochemical staining method and apoptotic index by TUNEL method. Results: 1. The expression of MMP-3 in mass was slightly higher in the SCC group (3.4±1.03) than the KA group (2.7±1.50). The expression of MMP-3 on the stroma was significantly higher for the SCC group (2.6±0.96) than the KA group (1.5±1.24) (p<0.05). 2. The expression of MMP-7 was detected only in a single case within the SCC group. 3. The expression of TIMP-1 was detected in two cases within the KA group. 4. The apoptotic index (%) was significantly higher in the SCC group (57.3± 32.15) than the KA group (36.1±21.78) (p<0.05). Conclusion: The immunohistochemical staining method of MMP-3, MMP-7 and TIMP-1 is not sensitive enough to differentiate between the two diseases. However, it has been suggested that MMP-3 of the stroma is involved in invasion of SCC more than MMP-3 of the mass, that MMP-7 plays a role in the early stage of SCC, and that TIMP-1 inhibits the action of MMPs and invasion in KA. We suggest that KA can be regarded as a clinically benign end of the SCC disease spectrum. The apoptotic index was higher in the SCC group than the KA group, implying that SCC has greater invasive ability due to a newly-selected, mutated, neoplastic cellular clone that has more aggressive biological behavior.