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Tytuł:
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Mutational profiling and immunohistochemical analysis of a surgical series of ampullary carcinomas.
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Autorzy:
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Harthimmer MR; Department of Pathology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Stolborg U; Department of Pathology, Odense University Hospital, Odense, Denmark.; Department of Pathology, Vejle Hospital, Vejle, Denmark.
Pfeiffer P; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.; Department of Oncology, Odense University Hospital, Odense, Denmark.; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
Mortensen MB; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.; Department of Surgery, Odense University Hospital, Odense, Denmark.
Fristrup C; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.; Department of Surgery, Odense University Hospital, Odense, Denmark.
Detlefsen S; Department of Pathology, Odense University Hospital, Odense, Denmark .; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
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Źródło:
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Journal of clinical pathology [J Clin Pathol] 2019 Nov; Vol. 72 (11), pp. 762-770. Date of Electronic Publication: 2019 Jun 29.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: London : BMJ Pub. Group
Original Publication: London : British Medical Association
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MeSH Terms:
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Biomarkers, Tumor*/analysis
Biomarkers, Tumor*/genetics
Gene Expression Profiling*
Immunohistochemistry*
Mutation*
Adenocarcinoma/*chemistry
Adenocarcinoma/*genetics
Ampulla of Vater/*chemistry
Digestive System Neoplasms/*chemistry
Digestive System Neoplasms/*genetics
Adenocarcinoma/pathology ; Adenocarcinoma/surgery ; Aged ; Aged, 80 and over ; Ampulla of Vater/pathology ; Ampulla of Vater/surgery ; Calcium-Binding Proteins/analysis ; Calcium-Binding Proteins/genetics ; Denmark ; Digestive System Neoplasms/pathology ; Digestive System Neoplasms/surgery ; Female ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microsatellite Instability ; Middle Aged ; Mucin 5AC/analysis ; Mucin 5AC/genetics ; Neoplasm Proteins/analysis ; Neoplasm Proteins/genetics ; Phenotype ; Predictive Value of Tests ; Registries ; Ribonucleoproteins, Small Nucleolar/analysis ; Ribonucleoproteins, Small Nucleolar/genetics ; Serpins/analysis ; Serpins/genetics
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Contributed Indexing:
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Keywords: ampullary carcinoma; immunohistochemistry; intestinal adenocarcinoma; next-generation sequencing; pancreatobiliary adenocarcinoma; subtyping
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Substance Nomenclature:
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0 (Biomarkers, Tumor)
0 (Calcium-Binding Proteins)
0 (IMP3 protein, human)
0 (MUC5AC protein, human)
0 (Mucin 5AC)
0 (Neoplasm Proteins)
0 (Ribonucleoproteins, Small Nucleolar)
0 (S100P protein, human)
0 (SERPIN-B5)
0 (Serpins)
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Entry Date(s):
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Date Created: 20190701 Date Completed: 20191101 Latest Revision: 20191101
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Update Code:
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20240104
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DOI:
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10.1136/jclinpath-2019-205912
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PMID:
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31256008
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Aims: Knowledge regarding the genetic features of ampullary carcinoma (AC) in European patients is limited. The utility of tumour markers for the establishment of a malignant diagnosis in biopsies from the ampullary region has not been fully elucidated. We aimed to describe the clinical, pathological, immunohistochemical (IHC) and genetic features of a Danish series of surgically resected ACs.
Methods: Surgically resected ACs (n=59) were examined regarding (1) clinicopathological features, (2) histological subtypes, (3) expression of IMP3, maspin, MUC5AC and S100P and (4) next-generation sequencing using a hybrid capture-based platform (Illumina HiSeq2500), including 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. Tumour mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.
Results: Pancreatobiliary adenocarcinomas (PB-AC), intestinal adenocarcinomas (INT-AC), other ampullary tumours and mixed adenocarcinomas represented 45.8%, 23.7%, 16.9% and 13.6%. The proportion of IHC-positive ACs (score ≥2) was: Maspin (94.9%), IMP3 (67.8%), S100P (39.0%) and MUC5AC (18.6%). Most frequently altered genes were TP53 (59.3%), KRAS (40.7%), APC (27.8%), SMAD4 (20.4%), CDKN2A (16.7%) and ARID2 / PIK3CA (each 11.1%). MUC5AC and S100P were frequently expressed in PB-AC, APC alterations frequent in INT-AC, SOX9 alterations were exclusive in INT-AC and MDM2 and FRS2 alterations in PB-AC. Four of 49 ACs (8.2%) were TMB-high/MSI-high and showed loss of MLH1 and PMS2.
Conclusions: PB-AC was the most frequent histological subtype of AC. Maspin and IMP3 were the IHC tumour markers with the highest sensitivity. Adenocarcinoma subtypes differed regarding several genetic alterations, whose predictive value remains to be evaluated.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
