Expression of G1/S-cyclins and cyclin-dependent kinase inhibitors in actinic keratosis and squamous cell carcinoma.
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, p16(INK4a) and p21(Cip1) (/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 p16(INK4a) . For cyclin E, central distribution dominated in SCC compared with the AK (p = 0.001) and SCCIS (p = 0.03). p21(Cip1) (/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 p16(INK4a) and p21(Cip1) (/Waf1) , respectively.


CONCLUSIONS
Our results suggest different alterations for p16(INK4a) and p21(Cip1) (/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.
Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Dimitrije
D
Brasanac
Clinic of Dermatovenereology, Clinical Center of Serbia, and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Jelena
J
Stojkovic-Filipovic
Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Martina
M
Bosic
Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Nada
N
Tomanovic
Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Emilija
E
Manojlovic-Gacic
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis*; D005260:Female; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055623:Keratosis, Actinic / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016196:S Phase; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D009363:Neoplasm Proteins
cyclin D1; cyclin E; p16; p21; squamous cell carcinoma