Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43927586" target="_blank" >RIV/00064173:_____/24:43927586 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/24:10485762 RIV/00216208:11120/24:43927586 RIV/00064165:_____/24:10485762

Result on the web

<a href="https://doi.org/10.1038/s41598-024-72687-3" target="_blank" >https://doi.org/10.1038/s41598-024-72687-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-024-72687-3" target="_blank" >10.1038/s41598-024-72687-3</a>

Result language

angličtina

Original language name

Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype

Original language description

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&apos; 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 &quot;non-intestinal&quot; 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30109 - Pathology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

14

Issue of the periodical within the volume

September

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

22241

UT code for WoS article

001354536300137

EID of the result in the Scopus database

2-s2.0-85205275902