-
Something wrong with this record ?
Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype
J. Hrudka, M. Kalinová, H. Fišerová, K. Jelínková, A. Nikov, P. Waldauf, R. Matěj
Language English Country England, Great Britain
Document type Journal Article
Grant support
Cooperatio Medical Diagnostics and Basic Medical Sciences
Univerzita Karlova v Praze
Cooperatio Medical Diagnostics and Basic Medical Sciences
Univerzita Karlova v Praze
Cooperatio Medical Diagnostics and Basic Medical Sciences
Univerzita Karlova v Praze
NLK
Directory of Open Access Journals
from 2011
Free Medical Journals
from 2011
Nature Open Access
from 2011-12-01
PubMed Central
from 2011
Europe PubMed Central
from 2011
ProQuest Central
from 2011-01-01
Open Access Digital Library
from 2011-01-01
Open Access Digital Library
from 2011-01-01
Health & Medicine (ProQuest)
from 2011-01-01
ROAD: Directory of Open Access Scholarly Resources
from 2011
Springer Nature OA/Free Journals
from 2011-12-01
- MeSH
- Adult MeSH
- Phenotype MeSH
- Class I Phosphatidylinositol 3-Kinases genetics metabolism MeSH
- Immunohistochemistry * MeSH
- Keratin-7 metabolism genetics MeSH
- Colorectal Neoplasms * genetics pathology metabolism mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Mucin-4 genetics metabolism MeSH
- Mucin 5AC genetics metabolism MeSH
- Mucin-6 genetics metabolism MeSH
- Mutation MeSH
- Biomarkers, Tumor * genetics metabolism MeSH
- Prognosis MeSH
- Proto-Oncogene Proteins B-raf genetics MeSH
- Proto-Oncogene Proteins p21(ras) genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Transcription Factors MeSH
- Matrix Attachment Region Binding Proteins * genetics metabolism MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
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.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24018849
- 003
- CZ-PrNML
- 005
- 20241024111113.0
- 007
- ta
- 008
- 241015s2024 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1038/s41598-024-72687-3 $2 doi
- 035 __
- $a (PubMed)39333321
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Hrudka, Jan $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Šrobárova 1150/50, Praha 10, 10034, Prague, Czech Republic. jan.hrudka@lf3.cuni.cz
- 245 10
- $a Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype / $c J. Hrudka, M. Kalinová, H. Fišerová, K. Jelínková, A. Nikov, P. Waldauf, R. Matěj
- 520 9_
- $a 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.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a kolorektální nádory $x genetika $x patologie $x metabolismus $x mortalita $7 D015179
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a lidé středního věku $7 D008875
- 650 _2
- $a senioři $7 D000368
- 650 12
- $a imunohistochemie $7 D007150
- 650 12
- $a nádorové biomarkery $x genetika $x metabolismus $7 D014408
- 650 12
- $a vazebné proteiny DNA v oblastech připojení k matrix $x genetika $x metabolismus $7 D036961
- 650 _2
- $a keratin-7 $x metabolismus $x genetika $7 D053552
- 650 _2
- $a prognóza $7 D011379
- 650 _2
- $a mucin 5AC $x genetika $x metabolismus $7 D055271
- 650 _2
- $a fenotyp $7 D010641
- 650 _2
- $a mucin 6 $x genetika $x metabolismus $7 D055272
- 650 _2
- $a mucin 4 $x genetika $x metabolismus $7 D055264
- 650 _2
- $a mutace $7 D009154
- 650 _2
- $a protoonkogenní proteiny B-Raf $x genetika $7 D048493
- 650 _2
- $a dospělí $7 D000328
- 650 _2
- $a senioři nad 80 let $7 D000369
- 650 _2
- $a fosfatidylinositol-3-kinasy třídy I $x genetika $x metabolismus $7 D058534
- 650 _2
- $a protoonkogenní proteiny p21(ras) $x genetika $7 D016283
- 650 _2
- $a vysoce účinné nukleotidové sekvenování $7 D059014
- 650 _2
- $a transkripční faktory $7 D014157
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Kalinová, Markéta $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Šrobárova 1150/50, Praha 10, 10034, Prague, Czech Republic $u Central Laboratories, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- 700 1_
- $a Fišerová, Hana $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Šrobárova 1150/50, Praha 10, 10034, Prague, Czech Republic
- 700 1_
- $a Jelínková, Karolína $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Šrobárova 1150/50, Praha 10, 10034, Prague, Czech Republic
- 700 1_
- $a Nikov, Andrej $u Department of General Surgery, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- 700 1_
- $a Waldauf, Petr $u Department of Anaesthesia and Intensive Care Medicine, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- 700 1_
- $a Matěj, Radoslav $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Šrobárova 1150/50, Praha 10, 10034, Prague, Czech Republic $u Department of Pathology, 1st Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic $u Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University, Thomayer University Hospital, Prague, Czech Republic
- 773 0_
- $w MED00182195 $t Scientific reports $x 2045-2322 $g Roč. 14, č. 1 (2024), s. 22241
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/39333321 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20241015 $b ABA008
- 991 __
- $a 20241024111107 $b ABA008
- 999 __
- $a ok $b bmc $g 2201612 $s 1230822
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 14 $c 1 $d 22241 $e 20240927 $i 2045-2322 $m Scientific reports $n Sci Rep $x MED00182195
- GRA __
- $a Cooperatio Medical Diagnostics and Basic Medical Sciences $p Univerzita Karlova v Praze
- GRA __
- $a Cooperatio Medical Diagnostics and Basic Medical Sciences $p Univerzita Karlova v Praze
- GRA __
- $a Cooperatio Medical Diagnostics and Basic Medical Sciences $p Univerzita Karlova v Praze
- LZP __
- $a Pubmed-20241015
