Targeted metabolomics shows plasticity in the evolution of signaling lipids and uncovers old and new endocannabinoids in the plant kingdom.

The remarkable absence of arachidonic acid (AA) in seed plants prompted us to systematically study the presence of C20 polyunsaturated fatty acids, stearic acid, oleic acid, jasmonic acid (JA), N-acylethanolamines (NAEs) and endocannabinoids (ECs) in 71 plant species representative of major phylogenetic clades. Given the difficulty of extrapolating information about lipid metabolites from genetic data we employed targeted metabolomics using LC-MS/MS and GC-MS to study these signaling lipids in plant evolution. Intriguingly, the distribution of AA among the clades showed an inverse correlation with JA which was less present in algae, bryophytes and monilophytes. Conversely, ECs co-occurred with AA in algae and in the lower plants (bryophytes and monilophytes), thus prior to the evolution of cannabinoid receptors in Animalia. We identified two novel EC-like molecules derived from the eicosatetraenoic acid juniperonic acid, an omega-3 structural isomer of AA, namely juniperoyl ethanolamide and 2-juniperoyl glycerol in gymnosperms, lycophytes and few monilophytes. Principal component analysis of the targeted metabolic profiles suggested that distinct NAEs may occur in different monophyletic taxa. This is the first report on the molecular phylogenetic distribution of apparently ancient lipids in the plant kingdom, indicating biosynthetic plasticity and potential physiological roles of EC-like lipids in plants.

Histopathological criteria and selection algorithms for BRCA1 genetic testing.

To ensure targeted treatment, it would be useful to know at the time of diagnosis whether a BRCA mutation is causally related to an individual breast cancer. The aim of this study was to investigate in an unselected series of breast cancer patients the value of incorporating morphological and immunohistochemical features for the selection of patients who may benefit from BRCA1 genetic testing. In a retrospective approach, histopathological results of tumors from 897 women were reevaluated regarding age at diagnosis, subtype of cancer, tumor grade, and estrogen (ER), progesterone (PR), and Her2/neu receptor status, as well as p53 and Ki67 status. In all, 142 tumors fulfilled morphological criteria indicative of a BRCA1 mutation. Of the 59 women willing to participate, 26 women concomitantly showed a positive family history. Pathogenic BRCA1 germline mutations were detected in 7 of 18 women (39%) (95% confidence interval = 0.17-0.64). All BRCA1-associated tumors were of high grade, invasive-ductal subtype, and PR and Her2/neu negative, and 91% of the tumors were negative for ER; 60% of the tumors showed a high expression of p53 and 60% a high expression of Ki67. There was a significant difference with respect to grading (P = 0.001 for G3), ER negativity (P = 0.0075), Ki67 > or = 65% (P = 0.0039), and triple negativity (i.e., ER(-), PR(-), Her2/neu(-)) (P = 0.0019) between tumors of mutation carriers and noncarriers.