T Nieto-Coronel, Ortega-Gómez Alette, R Yacab, E A Fernández-Figueroa, C Lopez-Camarillo, L Marchat, H Astudillo-de la Vega, E Ruiz-Garcia
{"title":"墨西哥 HER-2 过度表达乳腺癌患者外显子 9(E545K 和 E542K)和 20(H1047R)上的 PI3K 基因突变概况及其对临床病理和生存生物学影响的相关性。","authors":"T Nieto-Coronel, Ortega-Gómez Alette, R Yacab, E A Fernández-Figueroa, C Lopez-Camarillo, L Marchat, H Astudillo-de la Vega, E Ruiz-Garcia","doi":"10.1155/2024/9058033","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background</b>: Trastuzumab resistance is associated with overexpressing the human epidermal growth factor receptor 2 (HER-2), which results from the altered phosphoinositide 3-kinase (PI3K) pathway in breast cancer patients. <b>Objective</b>: We quantified the frequency of PI3K enzyme single and double-point mutations in Mexican patients with HER-2 overexpressing breast cancer and its association with clinical-pathological variables. <b>Methods</b>: We embedded HER-2 breast samples in paraffin from 60 patients, extracted their DNA, and evaluated PI3K mutations in 49 HER-2-positive breast tumors. We focused on mutations for one exon 20 (H1047R) and two exon 9 PI3K (E545K, E542K) hotspots and characterized them as single and double-point mutations. The mean patient follow-up was 86 months. <b>Results</b>: Of 49 patients who tested positive for HER-2 breast cancer, 14.28% showed mutations in PI3K, 71.42% single-point, and 28.56% double-point mutations. We found single-point mutations in H1047R (42.85%) and E545K (28.57%). Only two patients exhibited double-point mutations: one in E542K/E545K and another in H1047R/E545K (14.28% each). Although we observed lower survival in patients with mutations in PI3K, we did not find a significant association between these factors (<i>p</i> = 0.191). However, single and double-point mutations in PI3K were significantly associated with the clinical stages of diagnosis and tumor size (<i>p</i> = 0.027 and <i>p</i> = 0.04, respectively). <b>Conclusion</b>: Single and double-point mutations in PI3K are related to tumor size and advanced clinical-pathological traits in Mexican patients with HER-2 overexpression, and future molecular studies are necessary to understand these findings.</p>","PeriodicalId":46159,"journal":{"name":"International Journal of Breast Cancer","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496583/pdf/","citationCount":"0","resultStr":"{\"title\":\"PI3K Mutation Profiles on Exons 9 (E545K and E542K) and 20 (H1047R) in Mexican Patients With HER-2 Overexpressed Breast Cancer and Its Relevance on Clinical-Pathological and Survival Biological Effects.\",\"authors\":\"T Nieto-Coronel, Ortega-Gómez Alette, R Yacab, E A Fernández-Figueroa, C Lopez-Camarillo, L Marchat, H Astudillo-de la Vega, E Ruiz-Garcia\",\"doi\":\"10.1155/2024/9058033\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background</b>: Trastuzumab resistance is associated with overexpressing the human epidermal growth factor receptor 2 (HER-2), which results from the altered phosphoinositide 3-kinase (PI3K) pathway in breast cancer patients. <b>Objective</b>: We quantified the frequency of PI3K enzyme single and double-point mutations in Mexican patients with HER-2 overexpressing breast cancer and its association with clinical-pathological variables. <b>Methods</b>: We embedded HER-2 breast samples in paraffin from 60 patients, extracted their DNA, and evaluated PI3K mutations in 49 HER-2-positive breast tumors. We focused on mutations for one exon 20 (H1047R) and two exon 9 PI3K (E545K, E542K) hotspots and characterized them as single and double-point mutations. The mean patient follow-up was 86 months. <b>Results</b>: Of 49 patients who tested positive for HER-2 breast cancer, 14.28% showed mutations in PI3K, 71.42% single-point, and 28.56% double-point mutations. We found single-point mutations in H1047R (42.85%) and E545K (28.57%). Only two patients exhibited double-point mutations: one in E542K/E545K and another in H1047R/E545K (14.28% each). Although we observed lower survival in patients with mutations in PI3K, we did not find a significant association between these factors (<i>p</i> = 0.191). However, single and double-point mutations in PI3K were significantly associated with the clinical stages of diagnosis and tumor size (<i>p</i> = 0.027 and <i>p</i> = 0.04, respectively). <b>Conclusion</b>: Single and double-point mutations in PI3K are related to tumor size and advanced clinical-pathological traits in Mexican patients with HER-2 overexpression, and future molecular studies are necessary to understand these findings.</p>\",\"PeriodicalId\":46159,\"journal\":{\"name\":\"International Journal of Breast Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496583/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Breast Cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/2024/9058033\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Breast Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2024/9058033","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
PI3K Mutation Profiles on Exons 9 (E545K and E542K) and 20 (H1047R) in Mexican Patients With HER-2 Overexpressed Breast Cancer and Its Relevance on Clinical-Pathological and Survival Biological Effects.
Background: Trastuzumab resistance is associated with overexpressing the human epidermal growth factor receptor 2 (HER-2), which results from the altered phosphoinositide 3-kinase (PI3K) pathway in breast cancer patients. Objective: We quantified the frequency of PI3K enzyme single and double-point mutations in Mexican patients with HER-2 overexpressing breast cancer and its association with clinical-pathological variables. Methods: We embedded HER-2 breast samples in paraffin from 60 patients, extracted their DNA, and evaluated PI3K mutations in 49 HER-2-positive breast tumors. We focused on mutations for one exon 20 (H1047R) and two exon 9 PI3K (E545K, E542K) hotspots and characterized them as single and double-point mutations. The mean patient follow-up was 86 months. Results: Of 49 patients who tested positive for HER-2 breast cancer, 14.28% showed mutations in PI3K, 71.42% single-point, and 28.56% double-point mutations. We found single-point mutations in H1047R (42.85%) and E545K (28.57%). Only two patients exhibited double-point mutations: one in E542K/E545K and another in H1047R/E545K (14.28% each). Although we observed lower survival in patients with mutations in PI3K, we did not find a significant association between these factors (p = 0.191). However, single and double-point mutations in PI3K were significantly associated with the clinical stages of diagnosis and tumor size (p = 0.027 and p = 0.04, respectively). Conclusion: Single and double-point mutations in PI3K are related to tumor size and advanced clinical-pathological traits in Mexican patients with HER-2 overexpression, and future molecular studies are necessary to understand these findings.
期刊介绍:
International Journal of Breast Cancer is a peer-reviewed, Open Access journal that provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. The journal publishes original research articles, review articles, and clinical studies related to molecular pathology, genomics, genetic predisposition, screening and diagnosis, disease markers, drug sensitivity and resistance, as well as novel therapies, with a specific focus on molecular targeted agents and immune therapies.