CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation.

Autor: González-Martínez S; 'Contigo Contra el Cáncer de la Mujer' Foundation, 28010, Madrid, Spain.; Molecular Pathology of Cancer Group, Ramón y Cajal Health Research Institute (IRYCIS), 28034, Madrid, Spain.; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain., Kajabova VH; Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 84505, Bratislava, Slovakia., Pérez-Mies B; Molecular Pathology of Cancer Group, Ramón y Cajal Health Research Institute (IRYCIS), 28034, Madrid, Spain.; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain.; Department of Pathology, Ramón y Cajal University Hospital, 28034, Madrid, Spain.; Faculty of Medicine, University of Alcalá, 28801, Madrid, Spain., Carretero-Barrio I; Molecular Pathology of Cancer Group, Ramón y Cajal Health Research Institute (IRYCIS), 28034, Madrid, Spain.; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain.; Department of Pathology, Ramón y Cajal University Hospital, 28034, Madrid, Spain.; Faculty of Medicine, University of Alcalá, 28801, Madrid, Spain., Caniego-Casas T; Molecular Pathology of Cancer Group, Ramón y Cajal Health Research Institute (IRYCIS), 28034, Madrid, Spain.; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain., Sarrió D; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain.; Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols', Conexión Cáncer (UAM-CSIC), 28029, Madrid, Spain., Moreno-Bueno G; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain.; Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols', Conexión Cáncer (UAM-CSIC), 28029, Madrid, Spain.; MD Anderson Internacional Foundation, 28033, Madrid, Spain., Gión M; Department of Medical Oncology, Ramón y Cajal University Hospital, 28034, Madrid, Spain., Perez-García J; 'Contigo Contra el Cáncer de la Mujer' Foundation, 28010, Madrid, Spain.; International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron-salud Group, 08017, Barcelona, Spain.; Medica Scientia Innovation Research, 08007, Barcelona, Spain.; Medica Scientia Innovation Research, Ridgewood, NJ, 07450, USA., Cortés J; 'Contigo Contra el Cáncer de la Mujer' Foundation, 28010, Madrid, Spain.; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain.; International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron-salud Group, 08017, Barcelona, Spain.; Medica Scientia Innovation Research, 08007, Barcelona, Spain.; Medica Scientia Innovation Research, Ridgewood, NJ, 07450, USA.; Department of Medicine, Faculty of Biomedical and Health Sciences, European University of Madrid, 28670, Madrid, Spain.; IOB Institute of Oncology Madrid, Hospital Beata María Ana, Madrid, Spain., Smolkova B; Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 84505, Bratislava, Slovakia. bozena.smolkova@savba.sk., Palacios J; Molecular Pathology of Cancer Group, Ramón y Cajal Health Research Institute (IRYCIS), 28034, Madrid, Spain. jose.palacios@salud.madrid.org.; Centre for Biomedical Research in Cancer Networks (CIBERONC), Carlos III Health Institute, 28029, Madrid, Spain. jose.palacios@salud.madrid.org.; Department of Pathology, Ramón y Cajal University Hospital, 28034, Madrid, Spain. jose.palacios@salud.madrid.org.; Faculty of Medicine, University of Alcalá, 28801, Madrid, Spain. jose.palacios@salud.madrid.org.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2024 Aug; Vol. 485 (2), pp. 291-297. Date of Electronic Publication: 2024 May 07.
DOI: 10.1007/s00428-024-03814-8
Abstrakt: The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region. Few studies employing quantitative methods and covering CpG island shores, regions of relatively low CpG density situated proximal to conventional promoter CpGs, have been conducted, revealing lower percentages of methylation ranging from 0 to 51%. Therefore, using the quantitative pyrosequencing method, we examined CDH1 methylation in the island region and shores in E-cadherin deficient ILC cases (15 with CDH1 mutation and 22 non-mutated), 19 cases of invasive breast carcinomas non-special type (IBC-NSTs), and five cases of usual ductal hyperplasia (UDH). Our analysis revealed CDH1 methylation frequencies ranging from 3 to 64%, with no significant increase in methylation levels in any group of ILCs (median = 12%) compared to IBC-NST (median = 15%). In addition, considering the poorly studied association between the number of tumor-infiltrating lymphocytes (TILs) and CDH1 methylation in breast cancer, we undertook a thorough analysis within our dataset. Our findings revealed a positive correlation between CDH1 methylation and the presence of TILs (r = 0.5; p-value < 0.05), shedding light on an aspect of breast cancer biology warranting further investigation. These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in gene methylation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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