Cyclo-oxygenase type 2 is dysregulated in breast ductal carcinoma in situ and correlates with poor outcome

• Published in: European journal of obstetrics & gynecology and reproductive biology Vol. 151; no. 1; pp. 72 - 76
• Main Authors: de la Torre, Javier, Sabadell, M. Dolors, Rojo, Federico, Lirola, Jose Luis, Salicru, Sabina, Reventos, Jaume, Cajal, Santiago Ramón y, Xercavins, Jordi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.07.2010; Elsevier
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - metabolism; Breast; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - pathology; Carcinoma, Intraductal, Noninfiltrating - pathology; Cyclo-oxygenase type-2 (COX-2); Cyclooxygenase 2 - metabolism; Ductal Carcinoma in situ (DCIS); Female; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Mammary gland diseases; Medical sciences; Microinvasive carcinoma of the breast (MICB); Middle Aged; Obstetrics and Gynecology; Prognosis; Retrospective Studies; Tumors; Breast; Ductal Carcinoma in situ (DCIS); Prognosis; Cyclo-oxygenase type-2 (COX-2); Microinvasive carcinoma of the breast (MICB); Ductal carcinoma; Breast disease; Carcinoma in situ; Enzyme; Cyclooxygenase 2; Gynecology; In situ; Breast cancer; Malignant tumor; Breast ductal carcinoma in situ; Obstetrics; Oxygenase; Microinvasive; Mammary gland diseases; Oxidoreductases; Mammary gland; Cancer
• ISSN: 0301-2115; 1872-7654
• DOI: 10.1016/j.ejogrb.2010.02.033

Abstract Objective Clinico-pathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 2003 TNM criteria (T1mic ≤ 1 mm) 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. Study design 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. Condensation COX-2 as a molecular marker in microinvasive carcinoma of the breast.