PMID- 31256008
OWN - NLM
STAT- MEDLINE
DCOM- 20191101
LR  - 20191101
IS  - 1472-4146 (Electronic)
IS  - 0021-9746 (Linking)
VI  - 72
IP  - 11
DP  - 2019 Nov
TI  - Mutational profiling and immunohistochemical analysis of a surgical series of 
      ampullary carcinomas.
PG  - 762-770
LID - 10.1136/jclinpath-2019-205912 [doi]
AB  - 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.
CI  - (c) Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Harthimmer, Mads Rohde
AU  - Harthimmer MR
AD  - Department of Pathology, Odense University Hospital, Odense, Denmark.
AD  - Department of Clinical Research, Faculty of Health Sciences, University of 
      Southern Denmark, Odense, Denmark.
FAU - Stolborg, Uffe
AU  - Stolborg U
AD  - Department of Pathology, Odense University Hospital, Odense, Denmark.
AD  - Department of Pathology, Vejle Hospital, Vejle, Denmark.
FAU - Pfeiffer, Per
AU  - Pfeiffer P
AD  - Department of Clinical Research, Faculty of Health Sciences, University of 
      Southern Denmark, Odense, Denmark.
AD  - Department of Oncology, Odense University Hospital, Odense, Denmark.
AD  - Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
FAU - Mortensen, Michael Bau
AU  - Mortensen MB
AD  - Department of Clinical Research, Faculty of Health Sciences, University of 
      Southern Denmark, Odense, Denmark.
AD  - Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
AD  - Department of Surgery, Odense University Hospital, Odense, Denmark.
FAU - Fristrup, Claus
AU  - Fristrup C
AD  - Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
AD  - Department of Surgery, Odense University Hospital, Odense, Denmark.
FAU - Detlefsen, Sonke
AU  - Detlefsen S
AUID- ORCID: 0000-0002-9466-2333
AD  - Department of Pathology, Odense University Hospital, Odense, Denmark 
      sonke.detlefsen@rsyd.dk.
AD  - Department of Clinical Research, Faculty of Health Sciences, University of 
      Southern Denmark, Odense, Denmark.
AD  - Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
LA  - eng
PT  - Journal Article
DEP - 20190629
PL  - England
TA  - J Clin Pathol
JT  - Journal of clinical pathology
JID - 0376601
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (IMP3 protein, human)
RN  - 0 (MUC5AC protein, human)
RN  - 0 (Mucin 5AC)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Ribonucleoproteins, Small Nucleolar)
RN  - 0 (S100P protein, human)
RN  - 0 (SERPIN-B5)
RN  - 0 (Serpins)
SB  - IM
MH  - Adenocarcinoma/*chemistry/*genetics/pathology/surgery
MH  - Aged
MH  - Aged, 80 and over
MH  - Ampulla of Vater/*chemistry/pathology/surgery
MH  - *Biomarkers, Tumor/analysis/genetics
MH  - Calcium-Binding Proteins/analysis/genetics
MH  - Denmark
MH  - Digestive System Neoplasms/*chemistry/*genetics/pathology/surgery
MH  - Female
MH  - *Gene Expression Profiling
MH  - Genetic Predisposition to Disease
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - *Immunohistochemistry
MH  - Male
MH  - Microsatellite Instability
MH  - Middle Aged
MH  - Mucin 5AC/analysis/genetics
MH  - *Mutation
MH  - Neoplasm Proteins/analysis/genetics
MH  - Phenotype
MH  - Predictive Value of Tests
MH  - Registries
MH  - Ribonucleoproteins, Small Nucleolar/analysis/genetics
MH  - Serpins/analysis/genetics
OTO - NOTNLM
OT  - ampullary carcinoma
OT  - immunohistochemistry
OT  - intestinal adenocarcinoma
OT  - next-generation sequencing
OT  - pancreatobiliary adenocarcinoma
OT  - subtyping
COIS- Competing interests: None declared.
EDAT- 2019/07/01 06:00
MHDA- 2019/11/02 06:00
CRDT- 2019/07/01 06:00
PHST- 2019/04/18 00:00 [received]
PHST- 2019/06/08 00:00 [revised]
PHST- 2019/06/10 00:00 [accepted]
PHST- 2019/07/01 06:00 [pubmed]
PHST- 2019/11/02 06:00 [medline]
PHST- 2019/07/01 06:00 [entrez]
AID - jclinpath-2019-205912 [pii]
AID - 10.1136/jclinpath-2019-205912 [doi]
PST - ppublish
SO  - J Clin Pathol. 2019 Nov;72(11):762-770. doi: 10.1136/jclinpath-2019-205912. Epub 
      2019 Jun 29.