E-cadherin to P-cadherin switching in lobular breast cancer with tubular elements

Christgen, Matthias; Bartels, Stephan; Luttikhuizen, Jana Lisa van; Bublitz, Janin; Rieger, Luisa; Christgen, Henriette; Stark, Helge; Sander, Bjoern; Lehmann, Ulrich; Steinemann, Doris; Derksen, Patrick W.B.; Kreipe, Hans

doi:10.1038/s41379-020-0591-3

Cited by 32 publications

(67 citation statements)

References 46 publications

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“…Recently, a series of ILC with tubular elements representing the rare tubulo-lobular variant of ILC was investigated. The authors demonstrated the phenomenon of focal cadherin switching, wherein activation of P-cadherin, in an otherwise E-cadherin-negative tumour, rescued the function of the adherens junction enabling tubule formation [65]. Notably, co-incident LCIS did not express P-cadherin.…”

Section: What Is New In Invasive Lobular Carcinoma?mentioning

confidence: 99%

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

et al. 2021

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Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, tumours are luminal in molecular subtype, being oestrogen and progesterone receptor positive, and HER2 negative. Since last reviewing the lobular literature (McCart Reed et al., Breast Cancer Res 17:12, 2015), there has been a considerable increase in research output focused on this tumour type, including studies into the pathology and management of disease, a high-resolution definition of the genomic landscape of tumours as well as the evolution of several potential therapeutic avenues. There abounds a huge amount of new data, which we will review herein.

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Section: What Is New In Invasive Lobular Carcinoma?mentioning

confidence: 99%

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

et al. 2021

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“…BC of NST and ILC share a morphologic overlap. Cases in the morphologic overlap may be interpreted as (i) collision tumors, (ii) NST with lobular-like growth pattern but no loss of cell adhesion, and (iii) ILC with tubular elements [58,59]. For details, see text Section 2.3.…”

Section: Ilc As Carcinoma Growing In Single Filesmentioning

confidence: 99%

“…However, mutations in β-catenin/CTNNB1, which are not uncommon in various cancer entities and in some mesenchymal tumors [96][97][98], are consistently absent in ILC [43,99]. Whatever the mechanism, loss of E-cadherin is observed in 55-100% of cases (Appendix A, Table A2) [9][10][11][12][41][42][43]59,61,82,88,90,. CDH1 mutation, as determined by DNA sequencing, is observed in 12-85% of cases (Appendix A, Table A2).…”

Section: Ilc As a Morpho-molecular Entitymentioning

confidence: 99%

“…This is because the traditional meaning of "mixed BC (NST/ILBC)" describes a growth pattern and is restricted to the morphological level. From the perspective of a morpho-molecular tumor entity, mixed-appearing BCs may rather be interpreted as an assortment of: (i) collision tumors or genetically divergent subclones (id est, NST plus ILC), (ii) BCs of NST with lobularlike growth pattern but no molecular alterations related to cell adhesion, and (iii) ILCs with tubular elements (Figure 1C) [58,59]. However, there is also evidence that BCs with mixed-appearing histomorphology are not always collision tumors, and this exemplifies that every concept has certain limitations [58,129].…”

Section: Ilc As a Morpho-molecular Entitymentioning

confidence: 99%

“…Loss of E-cadherin, as determined by IHC, is observed in 55-100% of cases (Appendix A, Table A2) [9][10][11][12][41][42][43]59,61,82,88,90,. Aberrant fragmented, cytoplasmic or nuclear E-cadherin staining has been reported in as much as 16% and 35% of ILCs, respectively [109,124,197].…”

Section: Immunohistochemical Featuresmentioning

confidence: 99%

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Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

Christgen

Floris

Marchiò

et al. 2021

Cancers

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Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.

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Microenvironment‐induced restoration of cohesive growth associated with focal activation of P‐cadherin expression in lobular breast carcinoma metastatic to the colon

Gronewold,

Grote,

Bartels

et al. 2024

The Journal of Pathology CR

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Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E‐cadherin loss. Focal activation of P‐cadherin expression in tumor cells that are deficient for E‐cadherin occurs in a subset of ILCs. Switching from an E‐cadherin deficient to P‐cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52‐year‐old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E‐cadherin and P‐cadherin. CDH1/E‐cadherin mutations were determined by next‐generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E‐cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E‐cadherin‐negative and P‐cadherin‐negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter‐cryptal ILC cells switched to a P‐cadherin‐positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment‐induced EPS and conversion to cohesive growth.

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E-cadherin to P-cadherin switching in lobular breast cancer with tubular elements

Cited by 32 publications

References 46 publications

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

Microenvironment‐induced restoration of cohesive growth associated with focal activation of P‐cadherin expression in lobular breast carcinoma metastatic to the colon

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