Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial

Shuji Ogino*, Xiaoyun Liao, Yu Imamura, Mai Yamauchi, Nadine J. McCleary, Kimmie Ng, Donna Niedzwiecki, Leonard B. Saltz, Robert J. Mayer, Renaud Whittom, Alexander Hantel, Al B. Benson, Rex B. Mowat, Donna Spiegelman, Richard M. Goldberg, Monica M. Bertagnolli, Jeffrey A. Meyerhardt, Charles S. Fuchs

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Background Somatic mutations in PIK3CA (phosphatidylinositol-4,5- bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. Methods We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Results Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, diseasefree, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (Pinteraction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (Pinteraction > .16). Conclusions Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy.

Original languageEnglish (US)
Pages (from-to)1789-1798
Number of pages10
JournalJournal of the National Cancer Institute
Volume105
Issue number23
DOIs
StatePublished - Dec 4 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ogino, S., Liao, X., Imamura, Y., Yamauchi, M., McCleary, N. J., Ng, K., Niedzwiecki, D., Saltz, L. B., Mayer, R. J., Whittom, R., Hantel, A., Benson, A. B., Mowat, R. B., Spiegelman, D., Goldberg, R. M., Bertagnolli, M. M., Meyerhardt, J. A., & Fuchs, C. S. (2013). Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial. Journal of the National Cancer Institute, 105(23), 1789-1798. https://doi.org/10.1093/jnci/djt298