The Apoptosis and Expressions of p53, bcl-2, bax, PCNA, and cyclin D1 in Porokeratosis, Actinic Keratosis, and Squamous Cell Carcinoma

Choi, Yoo Won; Choi, Hae Young; Myung, Ki Bum

Abstract

BACKGROUND: Apoptosis is an important negative growth regulatory mechanism in tumors. In some malignancies, the apoptotic index(the percentage of apoptotic cells/bodies in the total number of tumor cells) may reflect the degree of carcinogeneity. In cells lacking functional p53, there is reduced susceptibility to apoptosis, thereby facilitating tumor growth. The bcl-2 gene product is a potent inhibitor of apoptosis and increases proliferation. The bcl-2/bax ratio is the critical determinant for the induction or inhibition of apoptosis. Proliferating cell nuclear antigen(PCNA) is present in nuclei throughout the cell cycle and is synthesized in the late G1 and S phases. Cyclin D1 is a major regulator of the G1 restriction point and may act as an oncogene; it is altered in several neoplasms. OBJECTIVE: Our purposes were to investigate the apoptotic index and the correlation between the apoptotic index and p53, bcl-2, bax, PCNA, and cyclin D1 in porokeratosis, actinic keratosis, and squamous cell carcinoma. METHODS: We investigated the apoptotic index by TUNEL and the expression of p53, bcl-2, bax, PCNA, and cyclin D1 by immunohistochemistry in 12 cases of porokeratosis, 18 cases of actinic keratosis, and 7 cases of squamous cell carcinomas. RESULTS: 1. The apoptotic index(%) in the epidermis central to the cornoid lamella was significantly higher than that of the peripheral epidermis in porokeratosis, 36.4+/-10.37 vs 24.4+/-8.76(p=0.004). 2. The apoptotic index(%) of actinic keratosis was significantly higher than that of porokeratosis, 37.4+/-7.73 vs 28.3+/-8.01(p=0.008). The apoptotic index(%) of squamous cell carcinoma was significantly higher than that of actinic keratosis, 45.1+/-6.18 vs 37.4+/-7.73(p=0.029). 3. p53 had significant positive correlation to the apoptotic index in porokeratosis and squamous cell carcinoma(p=0.002, 0.018). In actinic keratosis, the apoptotic index had significant positive correlation to cyclin D1(p=0.005). CONCLUSIONS: Actinic keratosis is more frequently evolved in malignant tumors than porokeratosis, which is supported by a significantly higher apoptotic index(%). Also the apoptotic index(%) of cutaneous malignant tumors was significantly higher than that of precancerous lesions. Apoptosis and p53, rather than proliferation, may provide the pathogenesis and progression into malignant tumors in porokeratosis. Apoptosis and cyclin D1 may provide the pathogenesis in actinic keratosis. In squamous cell carcinoma, p53-mediated apoptosis may be the key to pathogenesis in tumorigenesis and its proliferation.