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 ≤ 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.