title: Significance of cyclooxygenase 2, EZH-2 polycomb group and p53 expression in actinic keratosis and squamous cell carcinomas of the skin.
abstract: The development and progression of squamous cell carcinoma (SCC) of the skin is characterized by an accumulation of molecular changes. The aim of this study was to investigate the association of the immunohistochemical expression of cyclooxygenase-2 (COX-2), enhancer of zeste homolog 2 (EZH-2), and p53 in actinic keratosis (AK) and SCC and detect any differences between invasive and preinvasive squamous epidermal lesions. Forty-three cases with AK, 38 with SCC, and 9 with SCC arising on AK (SCC/AK) were studied. For COX-2 immunostaining, weak or no reaction was associated with AK (58.10% of cases), whereas moderate or strong reaction with SCCs (34.2% and 39.5%, respectively). Furthermore, 88.9% of the "mixed" SCC/AK specimens demonstrated moderate reaction (χ2 = 29.924, P < 0.0001). For EZH-2 immunostaining, a weak or no reaction was observed in 62.8% of AK cases, whereas a moderate reaction was observed in 42.1% of SCCs and 77.8% of "mixed" SCC/AK cases (χ2 = 18.91, P = 0.001). Weak immunoreactivity of p53 was associated with AK (58.1%), moderate with SCC (44.7%), and strong with SCC/AK lesions (66.7%) (χ2 = 15.999, P = 0.003). COX-2, p53, but mainly EZH-2 immune expression seems to be strongly associated with the biological potential of squamous epidermal cells and seems to be differentiating SCC by comparison to AK of the skin. The value of the combined expression of these markers is worth being further investigated as an additional tool for diagnostic, prognostic, and possibly, therapeutic use.
authors.affiliation: First Department of Pathology, Cytology and Dermatopathology Units, Medical School, National and Kapodestrian University of Athens, Athens, Greece.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Athanassiadou
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Lazaris
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Angelos
authors.initials: A
authors.lastname: Tsipis
authors.forename: George
authors.initials: G
authors.lastname: Chelidonis
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Aroni
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000032:analysis*; D003937:Diagnosis, Differential; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000201:enzymology* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000032:analysis*; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2