PIK3CA-AKT pathway mutations in micropapillary breast carcinoma
| Autor: | Daphne Ang, Christopher L. Corless, Carol Beadling, Megan L. Troxell, Ellen Flatley, Andrea Warrick |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Lymphovascular invasion Class I Phosphatidylinositol 3-Kinases DNA Mutational Analysis Breast Neoplasms Biology medicine.disease_cause Pathology and Forensic Medicine Phosphatidylinositol 3-Kinases medicine Carcinoma Biomarkers Tumor Humans Point Mutation Lymph node Aged Point mutation Carcinoma Ductal Breast Wild type DNA Neoplasm Ductal carcinoma Middle Aged medicine.disease Carcinoma Papillary medicine.anatomical_structure Lymphatic Metastasis Female KRAS Lymph Nodes Breast carcinoma Proto-Oncogene Proteins c-akt |
| Zdroj: | Human pathology. 44(7) |
| ISSN: | 1532-8392 |
| Popis: | Summary Micropapillary carcinoma of the breast is associated with increased rates of lymph node metastasis and lymphovascular invasion. While activating point mutations in PIK3CA (encoding phosphatidylinositol-3-kinase catalytic subunit) or AKT1 are found in 25% to 30% of invasive ductal carcinomas, the mutational profile of invasive micropapillary carcinomas has not been characterized in detail. Micropapillary carcinomas, concurrent metastatic and precursor breast lesions from 19 patients were identified. Lesional tissue was punched from paraffin-tissue blocks, and genomic DNA was extracted and screened for a large panel of known hotspot mutations using multiplex polymerase chain reaction and mass-spectroscopy analysis (643 mutations in 53 genes). Hotspot point mutations were identified in 35% (7/20) of micropapillary breast carcinomas, including PIK3CA exons 7, 9 and 20 hotspots, as well as the AKT1 plekstrin homology domain mutation (E17K); mutations in TP53 and KRAS were each found in a single patient. In 6 patients, micropapillary and non-micropapillary components of the same tumor were separately tested, yielding concordant results in five; one had a wild type micropapillary component, but a PIK3CA mutation in the invasive ductal component. Concurrent lymph node metastases were mostly wild type (2/8 mutant). Accompanying ductal carcinoma in situ had point mutations in 45% (5/11), mostly concordant with invasive carcinoma; however, mutational status of other breast proliferative lesions was generally discordant with accompanying carcinoma. The rate of PIK3CA mutations in this series of micropapillary carcinomas is similar to invasive ductal carcinomas; however, there may be an enrichment of AKT1 mutations (10%). The non-micropapillary components and precursor lesions occasionally had different mutations. |
| Databáze: | OpenAIRE |
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