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Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with β-catenin

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Backgrounds and aims

Lgr5 is a member of the G protein receptor super-family and was shown recently to be a stem cell marker for cells with intestinal differentiation. Its over-expression has been demonstrated in hepatocellular, basal cell carcinoma, and ovarian cancers but the underlying mechanisms are poorly understood. The aim of this study was to investigate if Lgr5 over-expression was correlated with human colorectal carcinogenesis and its potential correlation with β-catenin.

Methods

The study was carried out on a tissue microarray that consisted of 102 colorectal carcinomas (CRC; M:F = 55:47), 18 colon adenoma, and 12 colon normal mucosa cases. Immunostains were performed with the standard EnVision method with primary antibodies against Lgr5, β-catenin, and p53 antigens. Immunoreactivity of neoplastic cells to each antibody was double-blindly semi-quantified by two pathologists and the data were analyzed with the Chi-square and Spearman rank correlation tests. Subsequently, expression of Lgr5 in tissue sections of tumor centre and invasive margins of 21 cases of CRC certified to be immunoreactive of Lgr5 in TMA were evaluated and possible differences of Lgr5 expression between them were analyzed.

Results

Lgr5 immunoreactivity was observed only in single cells in the base of normal colon mucosal crypts but high in 28% (five out of 18) adenomas, and significantly higher in 54% (55/102, p = 0.016) CRC cases. In normal mucosa, adenoma, and CRC, β-catenin expression was seen in 25% (three out of 12), 27% (five out of 18), and 81% (83/102) cases, respectively, in contrast to 0, 0, and 40% (41/102) for p53 expression, respectively. In CRC, Lgr5 expression was more intense in women than men (p < 0.0001), and positively correlated with β-catenin expression (p < 0.001), but not with patients’ ages, tumor sizes, nodal status, TNM stages, and p53 expression. Different expression of Lgr5 between tumor centre and invasive margins was not found (p > 0.05).

Conclusions

The results suggest that up-regulation of Lgr5 expression, especially in female patients, may play an important role in colorectal carcinogenesis, probably through the WNT/β-catenin pathway, but not involve the progression of the CRC.

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Acknowledgments

The major results of this study were presented at the 2009 USCAP annual meeting and published in an abstract form in Modern Pathology. We are grateful to Dr. Biyun Xu for her expert assistance in statistical analysis. This study was supported by a grant from the Science and Technology Development Project of Nanjing City, Department of Science and Technology (No. 200601050).

Guarantor of the article

Xiangshan Fan, MD

Specific author contributions

Xiangshan Fan, MD: designed and executed the study; analyzed the results and wrote the manuscript draft.

Hongyan Wu, BS: performed immunohistochemistry

Qiang Zhou, BS: built the tissue microarray.

Hui-Ping Yu, MD: analyzed the results and performed statistical analysis

Yi Fen Zhang, MD: analyzed the results and scored the immunostains.

Qin Huang, MD, PhD: initiated the project, helped design the study, and wrote the manuscript.

Financial support

This project was supported by a grant from the Science and Technology Development Project of Nanjing City, Department of Science and Technology (No. 200601050)

Potential competing interests

None.

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Authors and Affiliations

  1. Department of Pathology, Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China

    Xiang-Shan Fan, Hong-Yan Wu, Hui-Ping Yu, Qiang Zhou, Yi-Fen Zhang & Qin Huang

  2. Department of Pathology and Laboratory Medicine, Harvard Medical School, Boston Veterans Affairs Healthcare System, 1400 VFW Parkway, West Roxbury, Boston, MA, 02132, USA

    Qin Huang

  3. Brown University Alpert Medical School, 1400 VFW Parkway, West Roxbury, Boston, MA, 02132, USA

    Qin Huang

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  1. Xiang-Shan Fan
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  2. Hong-Yan Wu
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Correspondence to Qin Huang.

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Fan, XS., Wu, HY., Yu, HP. et al. Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with β-catenin. Int J Colorectal Dis 25, 583–590 (2010). https://doi.org/10.1007/s00384-010-0903-z

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  • DOI: https://doi.org/10.1007/s00384-010-0903-z

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