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Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype
by
Matěj, Radoslav
, Kalinová, Markéta
, Waldauf, Petr
, Jelínková, Karolína
, Hrudka, Jan
, Nikov, Andrej
, Fišerová, Hana
in
692/4017
/ 692/4020
/ 692/4028
/ 692/53
/ Adenomatous polyposis coli
/ Adult
/ Aged
/ Aged, 80 and over
/ Amino acid sequence
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Cdc4 protein
/ Class I Phosphatidylinositol 3-Kinases - genetics
/ Class I Phosphatidylinositol 3-Kinases - metabolism
/ Claudin 18
/ Colorectal cancer
/ Colorectal carcinoma
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Cytokeratin
/ Cytokeratin 7
/ Female
/ Genetic analysis
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Immunohistochemistry
/ Intestine
/ K-Ras protein
/ Keratin-7 - genetics
/ Keratin-7 - metabolism
/ Male
/ Matrix Attachment Region Binding Proteins - genetics
/ Matrix Attachment Region Binding Proteins - metabolism
/ Medical prognosis
/ Middle Aged
/ Mucin
/ Mucin 5AC - genetics
/ Mucin 5AC - metabolism
/ Mucin-4 - genetics
/ Mucin-4 - metabolism
/ Mucin-6 - genetics
/ Mucin-6 - metabolism
/ Mucins
/ multidisciplinary
/ Mutation
/ Next-generation sequencing
/ NGS
/ p53 Protein
/ Phenotype
/ Phenotypes
/ Prognosis
/ Proto-Oncogene Proteins B-raf - genetics
/ Proto-Oncogene Proteins p21(ras) - genetics
/ SATB2
/ Science
/ Science (multidisciplinary)
/ Smad4 protein
/ Transcription Factors
2024
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Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype
by
Matěj, Radoslav
, Kalinová, Markéta
, Waldauf, Petr
, Jelínková, Karolína
, Hrudka, Jan
, Nikov, Andrej
, Fišerová, Hana
in
692/4017
/ 692/4020
/ 692/4028
/ 692/53
/ Adenomatous polyposis coli
/ Adult
/ Aged
/ Aged, 80 and over
/ Amino acid sequence
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Cdc4 protein
/ Class I Phosphatidylinositol 3-Kinases - genetics
/ Class I Phosphatidylinositol 3-Kinases - metabolism
/ Claudin 18
/ Colorectal cancer
/ Colorectal carcinoma
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Cytokeratin
/ Cytokeratin 7
/ Female
/ Genetic analysis
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Immunohistochemistry
/ Intestine
/ K-Ras protein
/ Keratin-7 - genetics
/ Keratin-7 - metabolism
/ Male
/ Matrix Attachment Region Binding Proteins - genetics
/ Matrix Attachment Region Binding Proteins - metabolism
/ Medical prognosis
/ Middle Aged
/ Mucin
/ Mucin 5AC - genetics
/ Mucin 5AC - metabolism
/ Mucin-4 - genetics
/ Mucin-4 - metabolism
/ Mucin-6 - genetics
/ Mucin-6 - metabolism
/ Mucins
/ multidisciplinary
/ Mutation
/ Next-generation sequencing
/ NGS
/ p53 Protein
/ Phenotype
/ Phenotypes
/ Prognosis
/ Proto-Oncogene Proteins B-raf - genetics
/ Proto-Oncogene Proteins p21(ras) - genetics
/ SATB2
/ Science
/ Science (multidisciplinary)
/ Smad4 protein
/ Transcription Factors
2024
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Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype
by
Matěj, Radoslav
, Kalinová, Markéta
, Waldauf, Petr
, Jelínková, Karolína
, Hrudka, Jan
, Nikov, Andrej
, Fišerová, Hana
in
692/4017
/ 692/4020
/ 692/4028
/ 692/53
/ Adenomatous polyposis coli
/ Adult
/ Aged
/ Aged, 80 and over
/ Amino acid sequence
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Cdc4 protein
/ Class I Phosphatidylinositol 3-Kinases - genetics
/ Class I Phosphatidylinositol 3-Kinases - metabolism
/ Claudin 18
/ Colorectal cancer
/ Colorectal carcinoma
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Cytokeratin
/ Cytokeratin 7
/ Female
/ Genetic analysis
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Immunohistochemistry
/ Intestine
/ K-Ras protein
/ Keratin-7 - genetics
/ Keratin-7 - metabolism
/ Male
/ Matrix Attachment Region Binding Proteins - genetics
/ Matrix Attachment Region Binding Proteins - metabolism
/ Medical prognosis
/ Middle Aged
/ Mucin
/ Mucin 5AC - genetics
/ Mucin 5AC - metabolism
/ Mucin-4 - genetics
/ Mucin-4 - metabolism
/ Mucin-6 - genetics
/ Mucin-6 - metabolism
/ Mucins
/ multidisciplinary
/ Mutation
/ Next-generation sequencing
/ NGS
/ p53 Protein
/ Phenotype
/ Phenotypes
/ Prognosis
/ Proto-Oncogene Proteins B-raf - genetics
/ Proto-Oncogene Proteins p21(ras) - genetics
/ SATB2
/ Science
/ Science (multidisciplinary)
/ Smad4 protein
/ Transcription Factors
2024
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Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype
Journal Article
Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype
2024
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Overview
Colorectal cancer (CRC) is a leading global cause of illness and death. There is a need for identification of better prognostic markers beyond traditional clinical variables like grade and stage. Previous research revealed that abnormal expression of cytokeratin 7 (CK7) and loss of the intestinal-specific Special AT-rich sequence-binding protein 2 (SATB2) are linked to poor CRC prognosis. This study aimed to explore these markers’ prognostic significance alongside two extraintestinal mucins (MUC5AC, MUC6), claudin 18, and MUC4 in 285 CRC cases using immunohistochemistry on tissue microarrays (TMAs). CK7 expression and SATB2-loss were associated with MUC5AC, MUC6, and claudin 18 positivity. These findings suggest a distinct \"non-intestinal\" immunohistochemical profile in CRC, often right-sided, SATB2-low, with atypical expression of CK7 and non-colorectal mucins (MUC5AC, MUC6). Strong MUC4 expression negatively impacted cancer-specific survival (hazard ratio = 2.7, p = 0.044). Genetic analysis via next-generation sequencing (NGS) in CK7 + CRCs and those with high MUC4 expression revealed prevalent mutations in
TP53, APC, BRAF, KRAS, PIK3CA, FBXW7,
and
SMAD4,
consistent with known CRC mutation patterns. NGS also identified druggable variants in
BRAF, PIK3CA,
and
KRAS
. CK7 + tumors showed intriguingly common (31.6%)
BRAF
V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 692/4020
/ 692/4028
/ 692/53
/ Adult
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Class I Phosphatidylinositol 3-Kinases - genetics
/ Class I Phosphatidylinositol 3-Kinases - metabolism
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Female
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Male
/ Matrix Attachment Region Binding Proteins - genetics
/ Matrix Attachment Region Binding Proteins - metabolism
/ Mucin
/ Mucins
/ Mutation
/ NGS
/ Proto-Oncogene Proteins B-raf - genetics
/ Proto-Oncogene Proteins p21(ras) - genetics
/ SATB2
/ Science
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