Co-expression of cytokeratin and vimentin in colorectal cancer highlights a subset of tumor buds and an atypical cancer-associated stroma

Meyer, Sara N.; Galván, José A.; Zahnd, Stefan; Sokol, Lena; Dawson, Heather; Lugli, Alessandro; Zlobec, Inti

doi:10.1016/j.humpath.2019.02.002

Cited by 31 publications

(25 citation statements)

References 25 publications

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“…It is well known that CK-20 is widely used for differential diagnosis between CRA, breast cancer, liver cancer, lung cancer, etc [7]. However, according to the current literature 10-20 % of CRA cases are CK-20negative [7,8] that is consistent with the obtained results (23,4 % of studied cases are CK-20- Furthermore, α-SMA-positive cells form so-called "tracks" which are directions for cancer cells movement [5,11,12].…”

Section: Abstract: Colorectal Cancer; Epithelial-mesenchymal Transitsupporting

confidence: 65%

Epithelial-mesenchymal transition and stem cells in colorectal cancer progression

Shyshkin

Khrystenko

2020

J Educ Health Sport

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Introduction. Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Studying invasion and metastasizing mechanisms in colorectal carcinogenesis is gaining momentum. The purpose of the study was to analyze immunohistochemical (IHC) expression levels of epithelial and mesenchymal phenotypic markers, as well as cancer stem cells markers on I-IV (pTNM) stages of CRC. Materials and

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Section: Abstract: Colorectal Cancer; Epithelial-mesenchymal Transitsupporting

confidence: 65%

Epithelial-mesenchymal transition and stem cells in colorectal cancer progression

Shyshkin

Khrystenko

2020

J Educ Health Sport

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“…Co-expression of E/M markers both in the primary breast cancer site and metastatic lymph nodes exhibited the worst survival rates among the patients [88]. Evidence showed tumour buds undergoing partial EMT in colorectal cancer patients [89]. Primary human high-grade serous ovarian cancer (HGSOC) tumour exhibited co-expression of E/M markers [90].…”

Section: Clinical Evidence Of Partial Emt In Human Cancersmentioning

confidence: 99%

“…EpCAM+, Cytokeratins+, E-cad+, Vimentin+, N-cad+, O-cad+, CD133+ [85] CTCs from women with metastatic BT Hybrid EMT Cytokeratins+, Vimentin+, N-cad+ [85] ESCC PT or MLN specimen from ESCC patients E-cad+, N-cad+, vimentin+ [86] CTC from early stage breast cancer patients stemness TWIST1+, CD44+, ALDH1+, EpCAM+ [87] Breast cancer samples from primary site and metastatic lymph nodes of breast cancer patients Co-expression of E/M markers E-cad+, vimentin+ [88] Human primary colorectal cancer specimen Cytokeratin+, vimentin+ [89] Primary HGSOC tumour E-cad+, vimentin+ [90] Primary AC, SCC tumours Vimentin+/cytokeratin+, E-cad+/N-cad+ [91] Abbreviations: ANKRD1, ankyrin repeat domain-containing protein 1; AOX1, aldehyde oxidase 1; COL3A1, collagen Type III α1 Chain; FGF2, fibroblast growth factor; LAMC2, laminin subunit γ 2; MME, membrane metallo-endopeptidase.…”

Section: Clinical Evidence Of Partial Emt In Human Cancersmentioning

confidence: 99%

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

et al. 2020

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Epithelial mesenchymal transition (EMT) is a complex process through which epithelial (E) cells lose their adherens junctions, transform into mesenchymal (M) cells and attain motility, leading to metastasis at distant organs. Nowadays, the concept of EMT has shifted from a binary phase of interconversion of pure E to M cells and vice versa to a spectrum of E/M transition states preferably coined as hybrid/partial/intermediate EMT. Hybrid EMT, being a plastic transient state, harbours cells which co-express both E and M markers and exhibit high tumourigenic properties, leading to stemness, metastasis, and therapy resistance. Several preclinical and clinical studies provided the evidence of co-existence of E/M phenotypes. Regulators including transcription factors, epigenetic regulators and phenotypic stability factors (PSFs) help in maintaining the hybrid state. Computational and bioinformatics approaches may be excellent for identifying new factors or combinations of regulatory elements that govern the different EMT transition states. Therapeutic intervention against hybrid E/M cells, though few, may evolve as a rational strategy against metastasis and drug resistance. This review has attempted to present the recent advancements on the concept and regulation of the process of hybrid EMT which generates hybrid E/M phenotypes, evidence of intermediate EMT in both preclinical and clinical setup, impact of partial EMT on promoting tumourigenesis, and future strategies which might be adapted to tackle this phenomenon.

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“…The resulting constraints are more difficult to accommodate in standard histopathology workflow. This is probably why the number of cases analyzed by IF approaches are often small (as mentioned in the Introduction) and mainly used for illustrative purposes in EMT studies [8][9][10]. On the contrary, the SCIM application we propose allows the analysis of E/M biomarkers co-expression in large series of tissue samples as well as easy morphological scrutiny.…”

Section: Discussionmentioning

confidence: 99%

“…Co-expression of epithelial and mesenchymal markers has also been evidenced in human cancer tissue samples, using different methodical approaches including immunofluorescence (IF), DepArray, and CyToF [8][9][10][11]. However, to the best of our knowledge, this co-expression was established for only a few cases, with a maximum of 18 cases in Navas et al [12] using an IF assay.…”

Section: Introductionmentioning

confidence: 99%

A Novel Approach for Quantifying Cancer Cells Showing Hybrid Epithelial/Mesenchymal States in Large Series of Tissue Samples: Towards a New Prognostic Marker

Godin

Balsat

Eycke

et al. 2020

Cancers

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In cancer biology, epithelial-to-mesenchymal transition (EMT) is associated with tumorigenesis, stemness, invasion, metastasis, and resistance to therapy. Evidence of co-expression of epithelial and mesenchymal markers suggests that EMT should be a stepwise process with distinct intermediate states rather than a binary switch. In the present study, we propose a morphological approach that enables the detection and quantification of cancer cells with hybrid E/M states, i.e., which combine partially epithelial (E) and partially mesenchymal (M) states. This approach is based on a sequential immunohistochemistry technique performed on the same tissue section, the digitization of whole slides, and image processing. The aim is to extract quantitative indicators able to quantify the presence of hybrid E/M states in large series of human cancer samples and to analyze their relationship with cancer aggressiveness. As a proof of concept, we applied our methodology to a series of about a hundred urothelial carcinomas and demonstrated that the presence of cancer cells with hybrid E/M phenotypes at the time of diagnosis is strongly associated with a poor prognostic value, independently of standard clinicopathological features. Although validation on a larger case series and other cancer types is required, our data support the hybrid E/M score as a promising prognostic biomarker for carcinoma patients.

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Co-expression of cytokeratin and vimentin in colorectal cancer highlights a subset of tumor buds and an atypical cancer-associated stroma

Cited by 31 publications

References 25 publications

Epithelial-mesenchymal transition and stem cells in colorectal cancer progression

Epithelial-mesenchymal transition and stem cells in colorectal cancer progression

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

A Novel Approach for Quantifying Cancer Cells Showing Hybrid Epithelial/Mesenchymal States in Large Series of Tissue Samples: Towards a New Prognostic Marker

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