Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma
© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd..
AIMS: The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions.
METHODS AND RESULTS: All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour.
CONCLUSIONS: A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
---|---|
Enthalten in: |
Histopathology - 84(2024), 6 vom: 25. Apr., Seite 1061-1067 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Kinzler, Maximilian N [VerfasserIn] |
---|
Links: |
---|
Themen: |
AGR2 protein, human |
---|
Anmerkungen: |
Date Completed 04.04.2024 Date Revised 04.04.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1111/his.15162 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM368997901 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM368997901 | ||
003 | DE-627 | ||
005 | 20240404234856.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240229s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1111/his.15162 |2 doi | |
028 | 5 | 2 | |a pubmed24n1364.xml |
035 | |a (DE-627)NLM368997901 | ||
035 | |a (NLM)38409827 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Kinzler, Maximilian N |e verfasserin |4 aut | |
245 | 1 | 0 | |a Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma |
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 04.04.2024 | ||
500 | |a Date Revised 04.04.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2024 The Authors. Histopathology published by John Wiley & Sons Ltd. | ||
520 | |a AIMS: The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions | ||
520 | |a METHODS AND RESULTS: All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour | ||
520 | |a CONCLUSIONS: A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a cholangiocarcinoma | |
650 | 4 | |a heterogeneity | |
650 | 4 | |a intrahepatic | |
650 | 4 | |a molecular | |
650 | 4 | |a pathology | |
650 | 4 | |a surgical oncology | |
650 | 7 | |a AGR2 protein, human |2 NLM | |
650 | 7 | |a Mucoproteins |2 NLM | |
650 | 7 | |a Oncogene Proteins |2 NLM | |
700 | 1 | |a Schulze, Falko |e verfasserin |4 aut | |
700 | 1 | |a Jeroch, Jan |e verfasserin |4 aut | |
700 | 1 | |a Schmitt, Christina |e verfasserin |4 aut | |
700 | 1 | |a Ebner, Silvana |e verfasserin |4 aut | |
700 | 1 | |a Gretser, Steffen |e verfasserin |4 aut | |
700 | 1 | |a Bein, Julia |e verfasserin |4 aut | |
700 | 1 | |a Finkelmeier, Fabian |e verfasserin |4 aut | |
700 | 1 | |a Trojan, Jörg |e verfasserin |4 aut | |
700 | 1 | |a Zeuzem, Stefan |e verfasserin |4 aut | |
700 | 1 | |a Schnitzbauer, Andreas A |e verfasserin |4 aut | |
700 | 1 | |a Demes, Melanie C |e verfasserin |4 aut | |
700 | 1 | |a Reis, Henning |e verfasserin |4 aut | |
700 | 1 | |a Wild, Peter J |e verfasserin |4 aut | |
700 | 1 | |a Walter, Dirk |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Histopathology |d 1985 |g 84(2024), 6 vom: 25. Apr., Seite 1061-1067 |w (DE-627)NLM000284408 |x 1365-2559 |7 nnns |
773 | 1 | 8 | |g volume:84 |g year:2024 |g number:6 |g day:25 |g month:04 |g pages:1061-1067 |
856 | 4 | 0 | |u http://dx.doi.org/10.1111/his.15162 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 84 |j 2024 |e 6 |b 25 |c 04 |h 1061-1067 |