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 III, 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

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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

Fingerprint

Colonic Neoplasms
Mutation
irinotecan
Leucovorin
Fluorouracil
Diphosphonates
Adjuvant Chemotherapy
Phosphatidylinositols
Exons
Phosphotransferases
Recurrence
Neoplasms
Microsatellite Instability
Molecular Pathology
Survival Analysis
Tumor Biomarkers
Oncogenes
Proportional Hazards Models
Colorectal Neoplasms
Catalytic Domain

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ogino, S., Liao, X., Imamura, Y., Yamauchi, M., McCleary, N. J., Ng, K., ... 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
Ogino, Shuji ; Liao, Xiaoyun ; Imamura, Yu ; Yamauchi, Mai ; McCleary, Nadine J. ; Ng, Kimmie ; Niedzwiecki, Donna ; Saltz, Leonard B. ; Mayer, Robert J. ; Whittom, Renaud ; Hantel, Alexander ; Benson III, Al B ; Mowat, Rex B. ; Spiegelman, Donna ; Goldberg, Richard M. ; Bertagnolli, Monica M. ; Meyerhardt, Jeffrey A. ; Fuchs, Charles S. / Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial. In: Journal of the National Cancer Institute. 2013 ; Vol. 105, No. 23. pp. 1789-1798.
@article{75072ad55a5f457893fdc4aad47068cc,
title = "Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial",
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.",
author = "Shuji Ogino and Xiaoyun Liao and Yu Imamura and Mai Yamauchi and McCleary, {Nadine J.} and Kimmie Ng and Donna Niedzwiecki and Saltz, {Leonard B.} and Mayer, {Robert J.} and Renaud Whittom and Alexander Hantel and {Benson III}, {Al B} and Mowat, {Rex B.} and Donna Spiegelman and Goldberg, {Richard M.} and Bertagnolli, {Monica M.} and Meyerhardt, {Jeffrey A.} and Fuchs, {Charles S.}",
year = "2013",
month = "12",
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language = "English (US)",
volume = "105",
pages = "1789--1798",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
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Ogino, S, Liao, X, Imamura, Y, Yamauchi, M, McCleary, NJ, Ng, K, Niedzwiecki, D, Saltz, LB, Mayer, RJ, Whittom, R, Hantel, A, Benson III, AB, Mowat, RB, Spiegelman, D, Goldberg, RM, Bertagnolli, MM, Meyerhardt, JA & Fuchs, CS 2013, 'Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial', Journal of the National Cancer Institute, vol. 105, no. 23, pp. 1789-1798. https://doi.org/10.1093/jnci/djt298

Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial. / Ogino, Shuji; Liao, Xiaoyun; Imamura, Yu; Yamauchi, Mai; McCleary, Nadine J.; Ng, Kimmie; Niedzwiecki, Donna; Saltz, Leonard B.; Mayer, Robert J.; Whittom, Renaud; Hantel, Alexander; Benson III, Al B; Mowat, Rex B.; Spiegelman, Donna; Goldberg, Richard M.; Bertagnolli, Monica M.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

In: Journal of the National Cancer Institute, Vol. 105, No. 23, 04.12.2013, p. 1789-1798.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Predictive and prognostic analysis of PIK3CA mutation in stage II colon cancer intergroup trial

AU - Ogino, Shuji

AU - Liao, Xiaoyun

AU - Imamura, Yu

AU - Yamauchi, Mai

AU - McCleary, Nadine J.

AU - Ng, Kimmie

AU - Niedzwiecki, Donna

AU - Saltz, Leonard B.

AU - Mayer, Robert J.

AU - Whittom, Renaud

AU - Hantel, Alexander

AU - Benson III, Al B

AU - Mowat, Rex B.

AU - Spiegelman, Donna

AU - Goldberg, Richard M.

AU - Bertagnolli, Monica M.

AU - Meyerhardt, Jeffrey A.

AU - Fuchs, Charles S.

PY - 2013/12/4

Y1 - 2013/12/4

N2 - 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.

AB - 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.

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U2 - 10.1093/jnci/djt298

DO - 10.1093/jnci/djt298

M3 - Article

VL - 105

SP - 1789

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JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

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