Back to Search
Start Over
E-cadherin to P-cadherin switching in lobular breast cancer with tubular elements
- Source :
- Modern Pathology
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Loss of E-cadherin expression due to mutation of the CDH1 gene is a characteristic feature of invasive lobular breast cancer (ILBC). Beta-catenin, which binds to the cytoplasmic domain of E-cadherin, is simultaneously downregulated, reflecting disassembly of adherens junctions (AJs) and loss of cell adhesion. E-cadherin to P-cadherin expression switching can rescue AJs and cell adhesion. However, P-cadherin has not been implicated in ILBC, so far. We aimed to characterize 13 ILBCs with exceptional histomorphology, which we termed ILBCs with tubular elements. The CDH1 mutational status was determined by next generation sequencing and whole-genome copy number (CN) profiling. Expression of cadherins was assessed by immunohistochemistry. ILBCs with tubular elements were ER-positive (13/13) and HER2-negative (13/13) and harbored deleterious CDH1 mutations (11/13) accompanied by loss of heterozygosity due to deletion of chromosome 16q22.1 (9/11). E-cadherin expression was lost or reduced in noncohesive tumor cells and in admixed tubular elements (13/13). Beta-catenin expression was lost in noncohesive tumor cells, but was retained in tubular elements (11/13), indicating focal rescue of AJ formation. N-cadherin and R-cadherin were always negative (0/13). Strikingly, P-cadherin was commonly positive (12/13) and immunoreactivity was accentuated in tubular elements. Adjacent lobular carcinoma in situ (LCIS) was always P-cadherin-negative (0/7). In a reference cohort of LCIS specimens, P-cadherin was constantly not expressed (0/25). In a reference cohort of invasive mammary carcinomas, P-cadherin-positive cases (36/268, 13%) were associated with triple-negative nonlobular breast cancer (P
- Subjects :
- Adult
0301 basic medicine
Pathology
medicine.medical_specialty
DNA Copy Number Variations
DNA Mutational Analysis
Lobular carcinoma
Gene Dosage
Loss of Heterozygosity
Breast Neoplasms
Article
Pathology and Forensic Medicine
CDH1
Loss of heterozygosity
Adherens junction
03 medical and health sciences
Breast cancer
0302 clinical medicine
Antigens, CD
Biomarkers, Tumor
medicine
Humans
RNA-Seq
Cell adhesion
Aged
biology
Cadherin
Middle Aged
Cadherins
medicine.disease
Immunohistochemistry
Gene Expression Regulation, Neoplastic
Carcinoma, Lobular
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
Cancer research
biology.protein
Female
Subjects
Details
- ISSN :
- 08933952
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Modern Pathology
- Accession number :
- edsair.doi.dedup.....aa6b645baa0c390743adb01451f183f1