An immunohistochemical characterization of basal cell carcinoma in patients below 40 years of age

BACKGROUND: Basal cell carcinoma (BCC) is the most common form of skin cancer, mainly occurring in the elderly. Studies on BCC patients under the age of 40 (early-onset BCC) are scarce. PATIENTS AND METHODS: 52 BCCs (48 patients, median age: 35 years) were investigated using immunohistochemistry, focusing on the cell cycle, immunogenicity, and HER2 expression. We used PCR to test for Human Papilloma Virus (HPV) and chromogenic in-situ hybridization for HER2 subclassification. RESULTS: 69% of cases were classified as non-aggressive subtypes, and 31% as aggressive. Changes in p16 and/or p53 were observed in 44% of cases. No HPV-DNA was detected. Overexpression of p16 was associated with an aggressive growth pattern, whereas p53 changes were independent of the growth pattern. Aggressive subtypes and p16-positivity correlated with higher expression levels of cyclin E1 and Ki-67, as well as a stronger B-cell response. Similar findings were observed in p53-altered basal cell carcinomas with respect to Ki-67 expression and B-lymphocyte infiltration; however, cyclin E1 expression was reduced in this subgroup. 71% of tumors belonged to the HER2-low group, which was associated with higher expression levels of cyclin E1 and Ki-67 and a more pronounced immunogenic response. CONCLUSIONS: This is the largest immunohistochemical characterization of early-onset BCC to date. The classification into non-aggressive and aggressive subtypes appears appropriate, as applied in the elderly. Further sub-classification based on p16, p53, and HER2 may reflect disrupted cell cycle mechanisms combined with an immunogenic response.