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PI3K Pathway Mutations and PTEN Levels in Primary and Metastatic Breast Cancer

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PI3K Pathway Mutations and PTEN Levels in Primary and Metastatic Breast Cancer

dc.contributor.author	González-Angulo, Ana María	es_ES
dc.contributor.author	Ferrer-Lozano, Jaime	es_ES
dc.contributor.author	Stemke-Hale, Katherine	es_ES
dc.contributor.author	Sahin, Aysegul	es_ES
dc.contributor.author	Liu, Shuying	es_ES
dc.contributor.author	Barrera, Juan A.	es_ES
dc.contributor.author	Burgues Gasión, Octavio	es_ES
dc.contributor.author	Lluch Hernández, Ana	es_ES
dc.contributor.author	Chen, Huiqin	es_ES
dc.contributor.author	Hortobagyi, Gabriel N.	es_ES
dc.contributor.author	Mills, Gordon B.	es_ES
dc.contributor.author	Meric-Bernstam, Funda	es_ES
dc.date.accessioned	2015-06-22T09:50:06Z
dc.date.available	2015-06-22T09:50:06Z
dc.date.issued	2011	es_ES
dc.identifier.citation	Molecular cancer therapeutics Vol. 10 Issue 6: pp. 1093-1101	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44663
dc.description.abstract	The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Fifty-micron paraffin sections were used for DNA extraction and 3-micron slides for immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). ER, PR and HER2 IHC were repeated in a central laboratory for both primary and metastasis. PTEN levels were assessed by IHC and PI3K pathway mutations detected by a mass spectroscopy-based approach. Median age was 48 years (range, 30 to 83 years). Tumor subtype included 72% hormone receptor-positive/HER2-negative, 20% HER2-positive, and less than 7.8% triple receptor negative. Tissues were available for PTEN IHC in 46 primary tumors and 52 metastases. PTEN was lost in 14 (30%) primary tumors and 13 (25%) metastases. There were 5 cases of PTEN loss and eight cases of PTEN gain from primary to metastasis (26% discordance). Adequate DNA was obtained on 46 primary tumors and on 50 metastases for PIK3CA analysis. PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases. There were five cases of PIK3CA mutation loss, and four cases of mutation gain (18% discordance). There was an increase of the level of PIK3CA mutations in four cases, and decrease in one from primary to metastasis. There is a high level of discordance in PTEN level, PIK3CA mutations, and receptor status between primary and metastatic disease that may influence patient selection and response to PI3K-targeted therapies.	es_ES
dc.subject	PIK3CA mutations	es_ES
dc.subject	PTEN loss	es_ES
dc.subject	Breast Cancer	es_ES
dc.subject	Metastasis	es_ES
dc.title	PI3K Pathway Mutations and PTEN Levels in Primary and Metastatic Breast Cancer	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1158/1535-7163.MCT-10-1089	es_ES
dc.identifier.idgrec	070443	es_ES