Cytokeratin 19 mRNA concentration in lymph nodes as a diagnostic marker of metastases

Ni, Rozhkova; Bozhenko, K. V.; Ploshnitsa, A. I.; Tashchyan, A. A.; Кудинова, Е А; Mazo, M. L.

doi:10.1007/s10517-008-0039-0

Cited by 2 publications

(3 citation statements)

References 5 publications

(2 reference statements)

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“…These gaps selectively favor monoclonal proliferation of the overlying tumor stem cells or progenitors if they are presentTumor stem cells or progenitors preferentially express high levels of cytokeratin 19, leading to the loss or reduction of the tumor capsule formation, and increased proliferation and mobility 64-65.Lymphocytes infiltrate the proliferating buds and disrupt intercellular junctions and surface adhesion molecules causing the dissociation of some cells from the buds and migration into the stroma.Within the stroma, different growth factors, including vascular endothelial growth factor and epidermal growth factor, stimulate proliferation of budding tumor stem cells leading to the formation of an endothelial cell lineage in responding to CK-19 expression-induced alterations 66-68.Lymphocyte infiltration also stimulates proliferation of the surrounding fibroblasts that harbor mesenchymal stem cells leading to the formation of an endothelial cell lineage 69.Due to their close physical proximity, stem cells within both the epithelial and stromal components equally contribute to newly formed vasculatures leading to the co-expression of D2-40 and CD34.…”

Section: Novel Findings and Hypothesismentioning

confidence: 99%

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Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

Jiang

Mason²,

Jewett³

et al. 2012

Int. J. Biol. Sci.

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Background: A great number of in vitro and in vivo studies have suggested that many pathways or factors can stimulate angiogenesis and lymphangiogenesis, which facilitate tumor progression and metastasis. However, the morphological and immunohistochemical profile of newly formed vasculatures has not been elucidated, making it difficult to differentiate them from the pre-existing ones, and to identify their unique molecular profiles for diagnosis and therapeutic interventions.Experimental findings: As cytokeratin (CK)-19 is a well-recognized stem cell marker and CK-19-positive cells are frequently detected in the peripheral blood of patients with metastatic cancer, our recent studies have assessed the involvement of CK-19 in the formation of new vasculatures in primary colorectal cancer (CRC) tissues. Our studies showed that a subset of lymph node-positive cases harbored some isolated normal epithelial structures with distinct CK-19 immunostaining within an otherwise CK-19-negative background. These structures are exclusively located within or adjacent to lymphoid follicles and are often surrounded by tube-like structures expressing lymphatic endothelial marker D2-40. Similar structures are more frequently seen at the junctions between pre-invasive and invasive CRC with the following features: (1). they consist of a single layer of endothelial cells that express both D2-40 and CD34, (2). their endothelial walls are often incomplete with disseminated cells protruding into the adjacent stroma, and (3). they are exclusively associated with disseminated CK-19-positive cellsHypothesis: Based on these findings, we propose that these tube-like structures represent newly formed vasculatures, which are derived by the convergence of aberrant lymphocyte infiltration and tumor stem cells. Because of their close physical proximity, tumor stem cells within the epithelial and stromal components contribute equally and coordinately to the morphogenesis of new vasculatures, which constitutes the basis for the unique morphologic and immunohistochemical features of newly formed vasculatures. Our hypothesis appears to be applicable to all epithelium-derived cancers.

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Section: Novel Findings and Hypothesismentioning

confidence: 99%

“…Tumor stem cells or progenitors preferentially express high levels of cytokeratin 19, leading to the loss or reduction of the tumor capsule formation, and increased proliferation and mobility 64-65.…”

Section: Novel Findings and Hypothesismentioning

confidence: 99%

Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

Jiang

Mason²,

Jewett³

et al. 2012

Int. J. Biol. Sci.

View full text Add to dashboard Cite

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“…CRC development and progression were shown to be complex processes that are associated with multiple genetic alterations [7]. One of these mutant molecules, cytokeratin 19 (CK19), is differentially expressed in the peripheral blood [8,9] and lymph nodes [10] of patients with breast cancer, or in epithelial cells of CRC patients with advanced Dukes' stage [11]. In addition, serum levels of the CK19 protein fragment CYFRA 21-1 were also evaluated in many cancers, and could represent a useful circulating tumor marker [12-14].…”

Section: Introductionmentioning

confidence: 99%

Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal malignancy

et al. 2009

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BackgroundColorectal cancer (CRC) is one of the leading causes of malignant death worldwide. Because young age of onset is often considered a poor prognostic factor for CRC, it is important to identify the poor outcomes of CRC in a younger population and to consider an aggressive approach by implementing early treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19) transcript from CRC patients and investigate its correlation with clinical stage, tumor malignancy, and age.MethodsThe quantitation of fecal CK19 transcript was determined by a quantitative real-time reverse transcription polymerase chain in 129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls. The levels of CK19 protein were examined both in colonic cell lines and tissues.ResultsThe analysis of 45 younger CRC patients (age ≤ 60 years) revealed that patients at the M1 stage had significantly higher expression levels of fecal CK19 mRNA when compared with healthy controls (p < 0.001) and patients at the M0 stage (p = 0.004). Additionally, the degree of consistency between the mean level of fecal CK19 mRNA and the distant metastatic rate in each age interval was up to 89% (p = 0.042).ConclusionThese results indicate that high levels of fecal CK19 mRNA represent a potential marker for colorectal malignancy and for aggressive treatment of younger CRC patients.

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Cytokeratin 19 mRNA concentration in lymph nodes as a diagnostic marker of metastases

Cited by 2 publications

References 5 publications

Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal malignancy

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