Expression of Lgr5 in Colorectal Carcinoma Correlates with That of -catenin: A Tissue Microarray Study
XS Fan, HP Yu, HY Wu, Q Zhou, Q Huang. Nanjing Drum Tower Hospital, Nanjing, China; Boston VA Healthcare System, Boston
Background: Lgr5 is a member of the G protein super-family and was shown recently to be a stem cell marker for cells with intestinal differentiation. Its over-expression has been demonstrated in colorectal carcinomas (CRC) but the underlying mechanisms remain unknown. The aim of this study was to investigate if Lgr5 was over-expressed in CRC in Chinese patients and if so, whether Lgr5 expression was correlated with -catenin for its involvement in CRC development through the WNT pathway.
Design: The study was carried out on a tissue microarray that consisted of 102 CRC (M:F=55:47), 18 (M:F=10:8) colon adenoma (CA), and 11 (M:F= 8:3) colon normal mucosa (CNM) cases. The tissue core was duplicated for each case. Immunostains were performed with a standard EnVision method with primary antibodies against Lgr5 (Lifespan Biosciences, 1:400), -catenin (Zymed Labs, 1:200), and p53 (Zymed Labs, 1:300) antigens. Immunoreactivity of cells was double-blindly semi-quantified by two pathologists and the data were compared with the Chi-square and Spearman rank correlation tests.
Results: Lgr5 immunoreactivity was observed only in single cells in the base of normal crypts but strong in 28% CA, and significantly higher in 54% (p=0.016) CRC cases. In CNM, CA, and CRC, -catenin immunoreactivity was seen in 25%, 27%, and 81% cases, respectively, in contrast to 0, 0, and 40% for p53 immunoreactivity, respectively. In CRC, Lgr5 expression was more common in women than men (p<0.0001), and positively correlated with -catenin expression (p<0.001), but not with patient ages, tumor sizes, nodal status, TNM stages, and p53 expression.
Conclusions: Intense Lgr5 expression was common in CRC, more frequent in female than male patients, and positively correlated with -catenin expression. The results suggest that Lgr5 may play an important role in CRC development in Chinese patients through the WNT pathway, which remains to be further investigated.
Monday, March 9, 2009 1:00 PM
Poster Session II # 69, Monday Afternoon