title: Expression of p300 and p300/CBP associated factor (PCAF) in actinic keratosis and squamous cell carcinoma of the skin.
abstract: p300 and p300/CBP-associated factor (PCAF) are histone modifiers and transcriptional co-factors involved in a number of cell processes. We investigated their expression patterns in 79 actinic keratoses (AK), 45 cases of Bowen's disease (BD), and 168 invasive squamous cell carcinomas of the skin (SCC). Using tissue microarray and immunohistochemistry, we evaluated p300 and PCAF expression in relation to the type of the lesion and SCC prognostic parameters (grade, diameter, thickness and level of invasion). High nuclear expression of p300 (>60% of positive cells) (p=0.001) and absent cytoplasmic expression (p=0.026) were more frequent in SCC compared to AK and BD, respectively. Cytoplasmic expression of p300 was associated with the SCC invasion of subcutaneous fat and deeper tissues (p=0.049). Diffuse distribution of cells with p300 nuclear expression was more commonly seen in BD and SCC compared to AK (p<0.001), in moderately- and poorly-differentiated SCC compared to well-differentiated SCC (p<0.001), in tumors thicker than 6mm (p<0.001), and in deeply invading tumors (p=0.001). More frequent loss of PCAF nuclear expression was observed in SCC than in AK and BD (p<0.001). Diffuse distribution of cells with PCAF cytoplasmic expression was more common in BD and SCC compared to AK (p<0.001), and in poorly-differentiated SCC compared to well- and moderately-differentiated SCC (p<0.001). Our results suggest that increase in nuclear expression of p300, as well as the presence of cytoplasmic but loss of nuclear expression of PCAF, could play an important role in the development and progression of cutaneous SCC.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: dr.martina@med.bg.ac.rs.
authors.forename: Martina M
authors.initials: MM
authors.lastname: Bosic
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Dimitrije C
authors.initials: DC
authors.lastname: Brasanac
authors.affiliation: Clinic for Dermatovenereology, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena M
authors.initials: JM
authors.lastname: Stojkovic-Filipovic
authors.affiliation: Institute of Histology and Embryology "Aleksandar Dj. Kostic", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Zaletel
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Jerad M
authors.initials: JM
authors.lastname: Gardner
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Sanja L
authors.initials: SL
authors.lastname: Cirovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism*; D046888:Tissue Array Analysis; D050880:p300-CBP Transcription Factors / Q000096:biosynthesis*; D000099224:p300-CBP-Associated Factor
chemical_list: D050881:E1A-Associated p300 Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494360:EP300 protein, human
keywords: Epithelial-mesenchymal transition; PCAF; Skin cancer; Tissue microarray; p300