J Cancer 2020; 11(13):3827-3833. doi:10.7150/jca.37437 This issue

Research Paper

Prevalence and characteristics of PIK3CA mutation in mismatch repair-deficient colorectal cancer

Weihua Li, Tian Qiu, Lin Dong, Fanshuang Zhang, Lei Guo, Jianming Ying

Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

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Li W, Qiu T, Dong L, Zhang F, Guo L, Ying J. Prevalence and characteristics of PIK3CA mutation in mismatch repair-deficient colorectal cancer. J Cancer 2020; 11(13):3827-3833. doi:10.7150/jca.37437. Available from https://www.jcancer.org/v11p3827.htm

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Background: Chromosomal instability (CIN) and microsatellite instability (MSI) account for the major causes of colorectal cancer (CRC). As an important component of the CIN pathway, PIK3CA mutation is a negative prognostic factor in CRC. However, the relationship between PIK3CA mutation and mismatch repair (MMR) status has not been well clarified.

Methods: MMR status was determined by immunohistochemical assay. KRAS, NRAS, BRAF, PIK3CA and TP53 mutations were comparatively analyzed in 424 MMR-proficient (pMMR) and 104 MMR-deficient (dMMR) CRC tumors using next-generation sequencing (NGS).

Results: PIK3CA mutation was more commonly mutated in dMMR tumors. PIK3CA mutation less commonly coexisted with KRAS/NRAS/BRAF and TP53 mutations, but more likely coexisted with HER2 and PTCH1 mutations in dMMR tumors compared with pMMR tumors. In tumors with concurrent RAS/BRAF and PIK3CA mutations, PIK3CA and RAS/BRAF mutant allele frequencies (MAFs) were highly concordant in dMMR tumors, whereas PIK3CA MAFs were significantly lower than the corresponding RAS/BRAF MAFs in pMMR tumors, implying that PIK3CA mutation may occur in the early stage of dMMR CRC.

Conclusions: The molecular pathogenesis is different between dMMR and pMMR tumors with PIK3CA mutation in CRC. PIK3CA mutation may act as a clonally dominant truncal mutation in dMMR CRC. Thus, combination of PIK3CA mutation and MMR status might determine a specific group of CRC to select treatment or elevate prognosis.

Keywords: PIK3CA mutation, MMR, colorectal cancer, RAS/BRAF mutations, next-generation sequencing