It has been known that p16, p21, and TGF-β are related to cellular proliferation and malignant transformation but the results of the previous studies are controversial.

This study was performed in order to investigate the possible role of p16, p21, and TGF-β in relation to the cellular proliferation and malignant transformation in various skin tumors.

For immunohistochemical staining we examined sections (4um thick) of formalin-fixed, paraffin-embedded tissue from 11 cases of squamous cell carcinoma (SCC), 13 cases of basal cell carcinoma (BCC), 7 cases of actinic keratosis, 5 cases of keratoacanthoma, and 4 cases of normal skin for control. Following conventional deparaffinization, the three step immunoperoxidase method was performed using the streptavidine-biotin complex and monoclonal antibodies. All sections were counterstained with hematoxylin. The expression of p16, p21, and TGF-β was evaluated and graded in relation to the intensity of cytoplasmic immunostaining of positive epidermal cells.

p16, p21, and TGF-β were detected mainly in the cytoplasm. The p21 positive cells were localized exclusively in the upper squamous layer and were not visualized in the basal layer. The expression of p21 was higher in SCC than BCC (P value=0.03). The expression of p21 in normal control was higher than skin tumors, but there was no significant difference among these tumors. There was a significant loss in the expression of p16 and TGF-β in various skin tumors compared with normal control, but no difference in the expression of p16 and TGF-β among these skin tumors.

1. p21 is possibly related to the differentiation of epidermal cells, because p21 was observed not in basal cells but in squamous and granular cells of the normal epidermis and the higher expression of p21 was demonstrated in SCC compared to BCC.

2. It may imply that loss of expression of p16 may play a critical role in malignant trans-formation but not in tumor progression of human malignant skin tumors, because the significant loss of the expression of p 16 was found in SCC and BCC when normal skin and there was no difference in the expression of p16 among various skin tumors but the expression of p16 of SCC is higher than that of actinic keratosis (P value=0.04).

3. It may imply that the loss of the expression of TGF-β may play a critical role in malignant transformation, because the significant loss of expression of TGF-β was found in various skin tumors when compared to normal skin, but there was no difference in the expression of TGF-β among various skin tumors.