IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas : Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia
© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd..
AIMS: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs.
METHODS AND RESULTS: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313).
CONCLUSIONS: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
|---|---|
| Enthalten in: |
Histopathology - 84(2024), 3 vom: 09. Jan., Seite 515-524 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Guerini, Camilla [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 10.01.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/his.15095 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36479660X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36479660X | ||
| 003 | DE-627 | ||
| 005 | 20240114233423.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/his.15095 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1255.xml |
| 035 | |a (DE-627)NLM36479660X | ||
| 035 | |a (NLM)37988281 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Guerini, Camilla |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas |b Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.01.2024 | ||
| 500 | |a Date Revised 10.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Histopathology published by John Wiley & Sons Ltd. | ||
| 520 | |a AIMS: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs | ||
| 520 | |a METHODS AND RESULTS: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313) | ||
| 520 | |a CONCLUSIONS: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a immune-mediated disorder | |
| 650 | 4 | |a non-conventional dysplasia | |
| 650 | 4 | |a small intestinal carcinoma | |
| 650 | 7 | |a DNA Modification Methylases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a Isocitrate Dehydrogenase |2 NLM | |
| 650 | 7 | |a EC 1.1.1.41 |2 NLM | |
| 650 | 7 | |a MGMT protein, human |2 NLM | |
| 650 | 7 | |a EC 2.1.1.63 |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Proteins |2 NLM | |
| 650 | 7 | |a DNA Repair Enzymes |2 NLM | |
| 650 | 7 | |a EC 6.5.1.- |2 NLM | |
| 650 | 7 | |a IDH1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.1.1.42. |2 NLM | |
| 700 | 1 | |a Furlan, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrario, Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Grillo, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Libera, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Arpa, Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a Klersy, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Lenti, Marco V |e verfasserin |4 aut | |
| 700 | 1 | |a Riboni, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Solcia, Enrico |e verfasserin |4 aut | |
| 700 | 1 | |a Fassan, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Mastracci, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Ardizzone, Sandro |e verfasserin |4 aut | |
| 700 | 1 | |a Moens, Annick |e verfasserin |4 aut | |
| 700 | 1 | |a De Hertogh, Gert |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrante, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Graham, Rondell P |e verfasserin |4 aut | |
| 700 | 1 | |a Sessa, Fausto |e verfasserin |4 aut | |
| 700 | 1 | |a Paulli, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Di Sabatino, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Vanoli, Alessandro |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Histopathology |d 1985 |g 84(2024), 3 vom: 09. Jan., Seite 515-524 |w (DE-627)NLM000284408 |x 0309-0167 |7 nnns |
| 773 | 1 | 8 | |g volume:84 |g year:2024 |g number:3 |g day:09 |g month:01 |g pages:515-524 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/his.15095 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 84 |j 2024 |e 3 |b 09 |c 01 |h 515-524 | ||