Supplementary Figure S2 from PIK3CA Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma

Holst, Frederik; Werner, Henrica M.J.; Mjøs, Siv; Hoivik, Erling A.; Kusonmano, Kanthida; Wik, Elisabeth; Berg, Anna; Birkeland, Even; Gibson, William J.; Halle, Mari K.; Trovik, Jone; Cherniack, Andrew D.; Kalland, Karl-Henning; Mills, Gordon B.; Singer, Christian F.; Krakstad, Camilla; Beroukhim, Rameen; Salvesen, Helga B.

doi:10.1158/1078-0432.22475442.v1

Supplementary Figure S2 from PIK3CA Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma

journal contribution

posted on 2023-03-31, 21:46 authored by Frederik Holst, Henrica M.J. Werner, Siv Mjøs, Erling A. Hoivik, Kanthida Kusonmano, Elisabeth Wik, Anna Berg, Even Birkeland, William J. Gibson, Mari K. Halle, Jone Trovik, Andrew D. Cherniack, Karl-Henning Kalland, Gordon B. Mills, Christian F. Singer, Camilla Krakstad, Rameen Beroukhim, Helga B. Salvesen

Relations between PIK3CA amplification status and expression of PI3K signaling related protein epitopes in 336 UCEC from BGCB including 29 and 41 tumors with polysomy 3 and focal PIK3CA amplification, respectively.

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ARTICLE ABSTRACT

Amplification of PIK3CA, encoding the PI3K catalytic subunit alpha, is common in uterine corpus endometrial carcinoma (UCEC) and linked to an aggressive phenotype. However, it is unclear whether PIK3CA amplification acts via PI3K activation. We investigated the association between PIK3CA amplification, markers of PI3K activity, and prognosis in a large cohort of UCEC specimens. UCECs from 591 clinically annotated patients including 83 tumors with matching metastasis (n = 188) were analyzed by FISH to determine PIK3CA copy-number status. These data were integrated with mRNA and protein expression and clinicopathologic data. Results were verified in The Cancer Genome Atlas dataset. PIK3CA amplifications were associated with disease-specific mortality and with other markers of aggressive disease. PIK3CA amplifications were also associated with other amplifications characteristic of the serous-like somatic copy-number alteration (SCNA)–high subgroup of UCEC. Tumors with PIK3CA amplification also demonstrated an increase in phospho-p70S6K but had decreased levels of activated phospho-AKT1-3 as assessed by Reverse Phase Protein Arrays and an mRNA signature of MTOR inhibition. PIK3CA amplification is a strong prognostic marker and a potential marker for the aggressive SCNA-high subgroup of UCEC. Although PIK3CA amplification associates with some surrogate measures of increased PI3K activity, markers for AKT1-3 and MTOR signaling are decreased, suggesting that this signaling is not a predominant pathway to promote cancer growth of aggressive serous-like UCEC. Moreover, these associations may reflect features of the SCNA-high subgroup of UCEC rather than effects of PIK3CA amplification itself.