PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer

Siv Mjos, Henrica M.J. Werner, Even Birkeland, Frederik Holst, Anna Berg, Mari K. Halle, Ingvild L. Tangen, Kanthida Kusonmano, Karen K. Mauland, Anne M. Oyan, Karl Henning Kalland, Aurélia E. Lewis, Gordon Mills, Camilla Krakstad, Jone Trovik, Helga B. Salvesen, Erling A. Hoivik

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Mutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with PIK3CA mRNA and phospho-AKT1 by gene expression and protein data, respectively. While PIK3CA mutations generally had no impact on survival, and were not associated with clinicopathological variables, patients with exon9 charge-changing mutations, providing a positive charge at the substituted amino acid residue, were associated with poor survival (p = 0.018). Furthermore, we characterized PIK3CA mutations in the metastatic setting, including 32 patients with matched primary tumors and metastases, and found a high level of concordance (85.7%; 6 out of 7 patients), suggesting limited heterogeneity. PIK3CA mRNA levels were increased in metastases compared to the primary tumors (p = 0.031), independent of PIK3CA mutation status, which rather associated with reduced PIK3CA mRNA expression. PIK3CA mutated tumors expressed higher p-AKT/AKT protein levels, both within primary (p < 0.001) and metastatic lesion (p = 0.010). Our results support the notion that the PI3K signaling pathway might be activated, both dependent- and independently of PIK3CA mutations, an aspect that should be considered when designing PIK3 pathway targeting strategies in endometrial cancer.

Original languageEnglish (US)
Article number10240
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer'. Together they form a unique fingerprint.

  • Cite this

    Mjos, S., Werner, H. M. J., Birkeland, E., Holst, F., Berg, A., Halle, M. K., Tangen, I. L., Kusonmano, K., Mauland, K. K., Oyan, A. M., Kalland, K. H., Lewis, A. E., Mills, G., Krakstad, C., Trovik, J., Salvesen, H. B., & Hoivik, E. A. (2017). PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer. Scientific Reports, 7(1), [10240]. https://doi.org/10.1038/s41598-017-10717-z