Cyclo-oxygenase type 2 is dysregulated in breast ductal carcinoma in situ and correlates with poor outcome.
OBJECTIVE
Clinico-pathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 2003 TNM criteria (T1mic</=1mm) are scarce. Nowadays, we do not know the percentages of Ductal Carcinoma in situ (DCIS) that will progress to invasion and predictive markers are not available. Cyclo-oxygenase type-2 (COX-2) is overexpressed in many human malignant tumours and has been linked to the processes of carcinogenesis, cell survival, invasion and metastasis. Despite the data on elevated COX-2 expression in breast neoplasia, the mechanism of upregulation remains unclear. This study aims to evaluate COX-2 expression in DCIS in comparison to MICB in order to establish the importance of this marker as a predictor of microinvasion and the correlation with Van Nuys classification.


METHODS
A retrospective study was performed on archival paraffin-embedded formalin-fixed tissue samples of DCIS and MICB from women who had undergone surgery. The COX-2 expression was assayed by immunohistochemistry using a specific polyclonal anti-human COX-2 antibody. Expression was scored in a scale 0 (absent) to 4 (strong) based on the extent and intensity of tumour cell staining.


RESULTS
Fifty-two cases of DCIS and 40 of MICB were studied. In all cases, COX-2 was detected in the cytoplasm of tumour cells, and elevated COX-2 expression was observed in Van Nuys high-grade CDIS cases compared with low and intermediate grades (p<0.05). In addition, enhanced COX-2 expression was significantly higher in DCIS component from MICB patients (82% cases) than in DCIS pure patients (40.4%) (p<0.05). In a multivariate model which includes age, tumour size, mammography, histological grade and COX-2 expression, we found COX-2 positivity to be an independent factor for microinvasion (OR 3.90; 95% CI 1.88-14.3).


CONCLUSIONS
COX-2 is associated to higher Van Nuys grades of breast CDIS, and could be a molecular marker to identify the cases of DCIS which could progress to MICB.


CONCLUSIONS
COX-2 as a molecular marker in microinvasive carcinoma of the breast.
Department of Pathology, Hospital Vall d'Hebron, Barcelona, Spain. javierdelat@gmail.com
Javier
J
de la Torre
M Dolors
MD
Sabadell
Federico
F
Rojo
Jose Luis
JL
Lirola
Sabina
S
Salicru
Jaume
J
Reventos
Santiago
S
Ramón y Cajal
Jordi
J
Xercavins
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human