Membranous ABCG2 expression in colorectal cancer independently correlates with shortened patient survival

Abstract

ABCG2 is a member of the ATP binding cassette (ABC) transporter superfamily and identified to play an important role in multidrug resistance in many studies. But the expression of ABCG2 is controversial in many kinds of tumors including colorectal cancer (CRC). To clarify the expression patterns of ABCG2 and elucidate the prognostic value of ABCG2 in CRC. ABCG2 expression was analyzed in 225 primary CRC tissues using immunohistochemical assessment. Cytoplasmic and membranous immunoreactivity were semiquantitatively scored and correlated with clinicopathological variables. 69 cases were used for survival analysis. χ2 test for trends, Kaplan-Meier analysis and Cox's regression were used for statistical analysis. 83.1% cases showed positive cytoplasmic expression including 13.3% strongly positive. 66.2% showed positive membranous expression including 15.6% strongly positive. 50% normal mucosa exhibited a strong membranous staining on the apical membrane. The strongly membranous staining significantly correlated to lymph node and distant metastasis. While the cytoplasmic expression levels of ABCG2 protein were only correlated with tumor stage. Survival analysis showed strongly membranous ABCG2 staining correlated to shortened patient survival than negative one (HR=2.439, 95%CI 1.053-5.650, P=0.038), but not cytoplasmic ABCG2 staining. Our results showed that membranous ABCG2 expression was significantly associated with Dukes' stage, lymph node metastasis and distant metastasis. However, cytoplasmic ABCG2 expression was only significantly associated with Dukes' stage. Strong membranous ABCG2 staining is a potential new independent prognostic factor of CRC. Further studies are needed to clarify the role of ABCG2 in colon carcinogenesis.