Expression of G1/S-cyclins and cyclin-dependent kinase inhibitors in actinic keratosis and squamous cell carcinoma

• Published in: Journal of cutaneous pathology Vol. 43; no. 3; pp. 200 - 210
• Main Authors: Brasanac, Dimitrije, Stojkovic-Filipovic, Jelena, Bosic, Martina, Tomanovic, Nada, Manojlovic-Gacic, Emilija
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2016
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; cyclin D1; cyclin E; Cyclin-Dependent Kinase Inhibitor Proteins - biosynthesis; Cyclins - biosynthesis; Female; G1 Phase; Gene Expression Regulation, Neoplastic; Humans; Keratosis, Actinic - metabolism; Keratosis, Actinic - pathology; Male; Middle Aged; Neoplasm Proteins - biosynthesis; p16; p21; S Phase; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; squamous cell carcinoma; cyclin E; cyclin D1; p16; p21; squamous cell carcinoma
• ISSN: 0303-6987; 1600-0560
• DOI: 10.1111/cup.12623

Background
Actinic keratosis (AK) and Bowen's disease (squamous cell carcinoma in situ, SCCIS) are pre‐invasive stages in the development of squamous cell carcinoma (SCC).
Methods
Immunohistochemical study of cyclin D1, cyclin E, p16INK4a and p21Cip1/Waf1 in AK (53 cases), SCCIS (16 cases) and SCC (40 cases), in relation to the type of the lesion and SCC prognostic parameters (grade, diameter and thickness).
Results
Diffuse cyclin D1 distribution was more frequent in SCCIS and SCC than in AK (p = 0.03) and similar pattern was observed for p16INK4a. For cyclin E, central distribution dominated in SCC compared with the AK (p = 0.001) and SCCIS (p = 0.03). p21Cip1/Waf1 displayed suprabasal distribution more frequently in AK than in SCCIS (p = 0.001) and SCC (p = 0.0004). Semiquantitative assessment showed more positive cells in AK (p = 0.04) and SCCIS (p = 0.04) than in SCC for cyclin E. SCC with diameter over 20 mm and those thicker than 6 mm revealed higher labeling index with p16INK4a and p21Cip1/Waf1, respectively.
Conclusions
Our results suggest different alterations for p16INK4a and p21Cip1/Waf1 in AK, SCCIS and SCC. Immunostaining distribution showed closer correlation with the type of the lesion, whereas percentage of positive cells displayed better association with the SCC prognostic parameters.