title: Prognostic value of COX-2, P53, and EZH-2 evaluated by quantitative image analysis in premalignant and malignant breast lesions.
abstract: BACKGROUND
  Cytological differential diagnosis of atypical hyperplasia and well differentiated breast carcinoma may be challenging, because sometimes there is an overlap between the cytomorphological features of these lesions. The aim of the study was to investigate COX-2, EZH-2, p53 expression in carcinomas and the gray zone of breast cytology categories of atypical hyperplastic lesions with regard to biological behavior of the tumor.
  
  
  METHODS
  FNA speciments from 100 patients with breast hyperplastic lesions and cancer were investigated by immunocytochemistry and a quantitative analysis for COX-2, p53, and EZH-2.
  
  
  RESULTS
  Extent of staining for COX-2 correlated with percentage of positive for EZH-2 (P < 0.0001) and p53 nuclei (P < 0.001). The intensity of COX-2 was lower in the carcinoma group (118.57 ± 12.43) than in the hyperplastic (127.16 ± 11.71) group (P = 0.006). On the contrary the mean value of staining extent was greater in the adenocarcinoma cases (15.96 ± 13.03) than in hyperplastic (4.04 ± 1.94) cases (P < 0.0001). The percentage of EZH-2 and p53 positive cells correlated with the histological type of the lesions (P = 0.001 and P = 0.011, respectively). There was also a statistically significant relation between tumor size and expression of COX-2 (P = 0.007) and EZH-2 (P = 0.010).
  
  
  CONCLUSIONS
  Our study showed that the expression of COX-2, EZH-2, and p53 as determined by immunocytochemistry at quantitative level may be a predictor for distinguishing cytologically atypical hyperplastic from malignant breast lesions and may be regarded as potential prognostic factor in breast cancer patients.
authors.affiliation: National and Kapodistrian University of Athens, School of Medicine, First Department of Pathology and Cytology Unit, 1st Pathology Laboratory, 11527, Athens, Greece.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Nicolopoulou-Stamati
authors.forename: Angelos
authors.initials: A
authors.lastname: Tsipis
authors.forename: George
authors.initials: G
authors.lastname: Chelidonis
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Pauline
authors.initials: P
authors.lastname: Athanassiadou
authors.forename: Maria
authors.initials: M
authors.lastname: Gonidi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Athanassiadou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D044963:Biopsy, Fine-Needle; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003937:Diagnosis, Differential; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
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
keywords: COX-2; EZH-2; malignant breast lesions; p53; quantitative image analysis