Stratifying Skin Cancer Patients and Guiding Treatment Decisions Through Combined p53 and p63 Expression Analysis

Skin cancer, particularly non-melanocytic types like squamous and basal cell carcinoma, remains a growing concern. The tumor suppressor proteins p53 and p63 play key roles in skin carcinogenesis. This study aimed to assess the differential expression of p53 and p63 in various stages of chemically-induced skin cancer.

FVB/N mice, aged 44 weeks, were randomly assigned into three groups: a control group (n=8) and two experimental groups (Group A: n=16, Group B: n=16). The study employed a two-stage carcinogenesis procedure, which involved an initial application of 97.4 nmol DMBA to shaved skin on the back, followed by applications of 32.4 nmol TPA after thirteen weeks for Group A and after twenty weeks for Group B. The control group did not receive any treatment. Skin lesions were monitored, and tissue samples were collected for histological and immunohistochemical analysis.

p53 expression was significantly elevated in precancerous and benign tumors compared to normal histology (47.6% and 47.8% vs. 18.8%, respectively; p<0.05), but not in malignant tumors. Mean p53 expression was significantly higher in both experimental groups compared to controls (group A: 42.1%, group B: 47.1%; p<0.001). Conversely, p63 expression remained generally low across all stages, with slightly higher levels in malignant lesions. The difference in expression between p53 and p63 was significant in precancerous and benign lesions (p<0.001). No significant differences in expression were found between the two experimental groups.

Distinct expression patterns of p53 and p63 suggest stage-specific roles in skin carcinogenesis. Elevated p53 in early lesions supports its tumor-suppressive function, while p63 may contribute to tumor maintenance in advanced stages. These findings support the utility of p53 and p63 as biomarkers for diagnosis and prognosis in skin cancer, and potential targets for future therapies.