دورية أكاديمية
أعرض في EDS

Immunohistochemical findings and clinicopathological features of breast cancers with pathogenic germline mutations in Non-BRCA genes.

التفاصيل البيبلوغرافية
العنوان: Immunohistochemical findings and clinicopathological features of breast cancers with pathogenic germline mutations in Non-BRCA genes.
المؤلفون: Singh K; Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Staff Pathologist, Women & Infants Hospital, 101 Dudley Street, Providence, RI, 02903, USA. Electronic address: 410jeeta@gmail.com., Scalia J; Genetics, Breast Health Center, Women & Infants Hospital, 101 Dudley Street, Providence, RI, 02903, USA., Legare R; Medical Oncology, Westerly Hospital, 25 Wells Street, Westerly, RI, 02903, USA., Quddus MR; Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Staff Pathologist, Women & Infants Hospital, 101 Dudley Street, Providence, RI, 02903, USA., Sung CJ; Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Staff Pathologist, Women & Infants Hospital, 101 Dudley Street, Providence, RI, 02903, USA.
المصدر: Human pathology [Hum Pathol] 2024 Apr; Vol. 146, pp. 49-56. Date of Electronic Publication: 2024 Apr 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: W B Saunders Country of Publication: United States NLM ID: 9421547 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8392 (Electronic) Linking ISSN: 00468177 NLM ISO Abbreviation: Hum Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: Philadelphia, PA : W B Saunders
Original Publication: Philadelphia, W B. Saunders Co.
مواضيع طبية MeSH: Breast Neoplasms*/genetics , Breast Neoplasms*/pathology , Germ-Line Mutation* , PTEN Phosphohydrolase*/genetics , Checkpoint Kinase 2*/genetics , Immunohistochemistry* , Ataxia Telangiectasia Mutated Proteins*/genetics , Fanconi Anemia Complementation Group N Protein*/genetics , Biomarkers, Tumor*/genetics , Biomarkers, Tumor*/analysis , Tumor Suppressor Proteins*/genetics, Humans ; Female ; Middle Aged ; Adult ; Aged ; Genetic Predisposition to Disease ; Nuclear Proteins/genetics
مستخلص: Deleterious germline mutations in multiple genes confer an increased breast cancer (BC) risk. Immunohistochemical (IHC) expression of protein products of mutated high-risk genes has not been investigated in BC. We hypothesized that pathogenic mutations may lead to an abnormal IHC expression pattern in the tumor cells. BCs with deleterious germline mutations in CHEK2, ATM, PALB2 & PTEN were identified. Immunohistochemistry was performed using Dako staining platform on formalin fixed paraffin embedded tumor tissue. Primary antibodies for PALB2 (ab202970), ATM [2C1(1A10)}, CHK2 (EPR4325), and PTEN (138G6) proteins were used for BCs with respective deleterious mutations. IHC expression was assessed in tumor and adjacent benign breast tissue. Total 27 BCs with 10 CHEK2, 9 ATM, 6 PALB2 & 2 PTEN deleterious germline mutations were identified. IHC staining was performed on 8 CHEK2, 7 ATM, 6 PALB2 & 2 PTEN cases. Abnormal CHEK2 IHC staining was identified in 7/8(88%) BCs. Three distinct CHK2 IHC patterns were noted: 1) Strong diffuse nuclear positivity (5 BC), 2) Null-pattern (2 BC), & 3) Normal breast-like staining in 1 BC Four of 5 (80%) strong CHK2 staining BC had missense CHEK2 mutations. Null-pattern was present with a missense & a frameshift mutation. Normal breast-like CHEK2 IHC staining pattern was present in 1 BC with CHEK2 frameshift mutation. Loss of nuclear/cytoplasmic PTEN IHC expression was noted in 2 in-situ carcinomas. Abnormal PTEN and CHK2 IHC were present in atypical ductal hyperplasia and flat epithelial atypia. ATM and PALB2 IHC expression patterns were similar in tumor cells and benign breast epithelium: mild to moderate intensity nuclear and cytoplasmic staining. We report abnormal CHEK2 IHC expression in 88% of BCs with pathogenic CHEK2 mutations. With PTEN and CHEK2 pathogenic mutations, abnormal IHC patterns are seen in early atypical proliferative lesions. IHC may be applied to identify CHEK2 & PTEN mutated BCs and precursor lesions.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Breast; Cancer; Gene; Immunohistochemistry; Protein
المشرفين على المادة: EC 3.1.3.67 (PTEN Phosphohydrolase)
EC 2.7.1.11 (Checkpoint Kinase 2)
EC 2.7.11.1 (CHEK2 protein, human)
EC 3.1.3.67 (PTEN protein, human)
EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
EC 2.7.11.1 (ATM protein, human)
0 (Fanconi Anemia Complementation Group N Protein)
0 (Biomarkers, Tumor)
0 (Tumor Suppressor Proteins)
0 (PALB2 protein, human)
0 (Nuclear Proteins)
تواريخ الأحداث: Date Created: 20240412 Date Completed: 20240504 Latest Revision: 20240504
رمز التحديث: 20240505
DOI: 10.1016/j.humpath.2024.04.004
PMID: 38608781
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-8392
DOI:10.1016/j.humpath.2024.04.004