Research Papers:

Hotspot KRAS exon 2 mutations in CD166 positive colorectal cancer and colorectal adenoma cells

Hung Lai Wong, Lawrence Po Wah Ng, Su Pin Koh, Lawrence Wing Chi Chan, Evelyn Yin Kwan Wong, Vivian Weiwen Xue, Hin Fung Andy Tsang, Amanda Kit Ching Chan, Ka Yue Chiu, Wah Cheuk and Sze Chuen Cesar Wong _

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Oncotarget. 2018; 9:20426-20438. https://doi.org/10.18632/oncotarget.24921

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Hung Lai Wong1, Lawrence Po Wah Ng2, Su Pin Koh1, Lawrence Wing Chi Chan1, Evelyn Yin Kwan Wong1, Vivian Weiwen Xue1, Hin Fung Andy Tsang1, Amanda Kit Ching Chan2, Ka Yue Chiu2, Wah Cheuk2 and Sze Chuen Cesar Wong1

1Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region

2Department of Pathology, Queen Elizabeth Hospital, Kowloon Central Cluster, Hospital Authority, Hong Kong Special Administrative Region

Correspondence to:

Sze Chuen Cesar Wong, email: [email protected]

Keywords: colorectal cancer; colorectal adenoma; CD166; KRAS exon 2 mutations; immunohistochemical staining

Received: July 18, 2017     Accepted: January 20, 2018     Published: April 17, 2018


Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Recent studies have shown that cancer stem cells (CSCs) are an important cause of tumor recurrence and metastasis. We hypothesized that CSCs marker CD166-positive CRC and colorectal adenoma (CAD) cells consist of more hotspot mutations than CD166-negative CRC and colorectal adenoma cells. To verify this, formalin fixed paraffin embedded tissue specimens from 42 patients each with CRC and CAD were recruited and CD166 immunohistochemical (IHC) staining followed by macrodissection was performed. DNA extracted was used for quantitative polymerase chain reaction detection on a somatic mutation array. Results showed that the immunoreactivity of CD166 protein had significant difference among CRC, CAD, and normal colorectal epithelial tissues (NCET) (P < 0.0001, Kruskal-Wallis test). Moreover, nucleotide changes were found in APC, KRAS, P53, PIK3CA, FBXW7 and SRC genes. Among those genes, KRAS exon 2 mutations were validated in another cohort of 70 CRC and 72 CAD specimens. Results showed that the difference in percentage of KRAS exon 2 mutations between CD166 positive and CD166 negative CRC specimens was significant (P < 0.05, chi-square test). Long term follow-up of the CRC patients showed that CD166-positive KRAS exon 2 mutations was useful in discriminating CRC patients with worse outcome. This study has provided evidence that KRAS exon 2 mutations are concentrated in CD166-positive cancer cells, with prognostic significance in CRC, and those mutations are also detected in CAD.

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