Actinic keratosis with severe dysplasia and Bowen disease represent distinct pathways of intraepidermal squamous neoplasia: an immunohistochemical study

Intraepidermal squamous neoplasia is a precursor to invasive cutaneous squamous cell carcinoma. The most common type of intraepidermal squamous neoplasia is actinic keratosis (AK), although there is compelling clinicopathological evidence of a second distinct pattern of squamous dysplasia termed Bowen disease (BD). The distinction between these pathways of dysplasia has been inconsistently delineated in the literature. To further investigate the biological differences between AK and BD, a cohort of cases of intraepidermal squamous dysplasia including AK with mild/moderate dysplasia (n=26), AK with severe dysplasia (n=21) and BD (n=47) was prospectively collected. Immunohistochemistry was utilised to assess the protein expression of major tumour suppressor genes including p16, RB-1 and p53. Most cases of BD showed complete loss of RB-1 (∼80%), strong and diffuse positive staining for p16 (∼80%) ​and mutant pattern (diffusely positive or completely negative) of p53 (∼79%). However, lesions of AK showed loss of RB-1 in only 6%, strong and diffuse positive staining for p16 in 4% and mutant pattern of p53 in 85% of case (p<0.001). The statistically significant difference in RB-1 and p16 expressions between AK and BD confirms that the two morphologically distinct types of intraepidermal squamous neoplasia differ in protein expression of major tumour suppressor genes and provide evidence that they represent two distinct genomic pathways of squamous neoplasia. Recognition of clinical and genomic differences between different pathways of squamous neoplasia could potentially have an important role in predicting the biological behaviour and treatment of advanced tumours arising from these precursor lesions.