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Proffered Abstract (Plenary Session): Determinants of Patient Prognosis

CEACAM: A potential novel predictor of breast cancer recurrence

St James's University Hospital, Leeds, United Kingdom and Leeds General Infirmary, Leeds, United Kingdom

Abstract

PR-8

Introduction:Members of the CEACAM family have been previously described as aggressive markers in colorectal, gastric and pancreatic tumors. The aim of this study was to examine expression of this molecule in endocrine sensitive and relapsed breast tumors using microarray technology and validation on tissue microarrays (TMA).Methods:An in vitro model of tamoxifen resistance was established by continuous culture in 4-hydroxytamoxifen. These cells were subjected to gene expression analysis using the Affymetrix U133A gene chip. Subsequently, a TMA was constructed using 119 tamoxifen-relapsed human breast cancers and 281 tamoxifen sensitive controls. After accounting for core loss and cores lacking invasive disease, there were 105 and 247 cases respectively. From the 105 cases available for analysis, 68 represented pathology on initial presentation, whereas the remainder represented episodes of recurrence. Calculations for the probability of recurrence were based on these 68 cases only. The remainder was used for intra-group examination. TMA sections were stained with CEACAM 5&6 antibody (Abcam) and scored according to cytoplasmic and membrane staining with a maximum score of 3 indicating strong staining in >10% of cells.Results:Affymetrix gene expression analysis revealed differential regulation of 287 genes in tamoxifen resistant cells compared to controls. Of interest was an observed 19 fold up-regulation in CEACAM6. This observation was confirmed by RT-PCR.Immunohistochemical results revealed that 37/68 (54%) of tamoxifen-relapsed tumors demonstrated moderate to strong expression of CEACAM compared with 56/247 of controls, OR = 4.07 (95% CI 2.32 to 7.15). This was highly significant, with an absolute difference = 31%, (p<0.0001; 95% CI 19 to 43). Findings were independent of tumor size, ER and HER-2 expression (p<0.001).Conclusion:This is the first report of CEACAM expression in breast cancer. Our results show a strong association with recurrence that is independent of several histopathological factors.