Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.
Adenocarcinoma
/ diagnosis
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Colonic Neoplasms
/ diagnosis
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Membrane Glycoproteins
/ genetics
Middle Aged
Neoplasm Staging
Oncogene Fusion
Oncogene Proteins, Fusion
/ genetics
Receptor Protein-Tyrosine Kinases
/ genetics
Receptor, trkA
/ genetics
Receptor, trkB
/ genetics
Receptor, trkC
/ genetics
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
pubmed:
1
10
2019
medline:
14
5
2020
entrez:
1
10
2019
Statut:
ppublish
Résumé
This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median age: 63 y). The tumors involved the right (n=12) and left colon unequally and were either stage T3 (n=12) or T4. Local lymph node and distant metastases were seen at presentation in 6 and 1 patients, respectively. Lymphovascular invasion was present in all cases. Histologically, tumors showed moderate to poor (n=11) differentiation with a partly or entirely solid pattern (n=5) and mucinous component (n=10), including 1 case with sheets of signet ring cells. DNA mismatch repair-deficient phenotype was seen in 13 cases. Tumor-infiltrating CD4/CD8 lymphocytes were prominent in 9 cases. Programmed death-ligand 1 positive tumor-infiltrating immune cells and focal tumor cell positivity were seen in the majority of cases. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 cases. No mutations in BRAF, RAS, and PIK3CA were identified. However, other genes of the PI3K-AKT/MTOR pathway were mutated. In several cases, components of Wnt/β-catenin (APC, AMER1, CTNNB1), p53, and TGFβ (ACVR2A, TGFBR2) pathways were mutated. However, no SMAD4 mutations were found. Two tumors harbored FBXW7 tumor suppressor gene mutations. NTRK fusion tumors constitute a distinct but rare subgroup of colorectal carcinomas.
Identifiants
pubmed: 31567189
doi: 10.1097/PAS.0000000000001377
pii: 00000478-202002000-00003
pmc: PMC8170835
mid: NIHMS1538540
doi:
Substances chimiques
Biomarkers, Tumor
0
Membrane Glycoproteins
0
Oncogene Proteins, Fusion
0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Receptor, trkA
EC 2.7.10.1
Receptor, trkB
EC 2.7.10.1
Receptor, trkC
EC 2.7.10.1
tropomyosin-related kinase-B, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
162-173Subventions
Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011427
Pays : United States
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