4 research outputs found
HER-2 status determination in breast carcinomas. A practical approach
Accurate evaluation of HER-2 status is
crucial in the selection of breast carcinoma patients for
trastuzumab (Herceptin) treatment. Various laboratory
methods have been used for this purpose. The aim of the
present work was to analyse the results obtained in the
routine practice by immunohistochemistry (IHC) and
fluorescence in situ hybridization (FISH) in
determination of HER-2 status. Five hundred and three
cases of breast invasive ductal carcinoma were selected
to analyse the HER-2 overexpression by
immunohistochemistry (HercepTest, Dako). HercepTest
2+ equivocal cases (60) were studied by FISH
(PathVysion, Vysis) to determine HER-2 gene
amplification. HER-2 overexpression determined by
Herceptest was shown in 97/503 cases (19%). FISH
performed on equivocal cases demonstrated HER-2
amplification in 11/60 tumours (18%). IHC and FISH
together showed HER-2 overexpression / gene
amplification in 21% of breast invasive carcinomas.
Immunohistochemical determination of HER-2 status
represents an easy and standardized method that (in
contrast to FISH) can be performed in all pathology
laboratories without need of any special microscope and enabling to check the morphologic features of the cells
analysed. However, in order to assure the reliability of
the results, standardization of fixation protocols,
automation of the immunohistochemical procedure, and
training of pathologists in the interpretation of the results
(scoring criteria) should be a priority. Equivocal
HercepTest cases must be analysed by FISH preferably
in a reference laboratory
Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment
Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death
Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment
Altres ajuts: Fundación Científica de la AECC (to R.G.U.); Fundación Ramón Areces (to M.F.F); FICYT (to E.G.T., M.G.G., A.C.); Asturias Regional Government [GRUPIN14-052 to M.F.F.]; Gobierno del Principado de Asturias, PCTI-Plan de Ciencia, Tecnología e Innovación co-funding Fondos FEDER (grant number IDI/2018/146 to M.F.F. and IDI/2018/144 to C.L.); Asociación Española Contra el Cáncer [AECC-CI-2015]; P.M. acknowledges financial support from The Obra Social La Caixa-Fundaciò Josep Carreras. P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain.Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death