ABSTRACT
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/ß-catenin (APC, AMER1, CTNNB1), p53, and TGFß (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.
Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , Receptor Protein-Tyrosine Kinases/genetics , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Colonic Neoplasms/pathology , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Middle Aged , Neoplasm Staging , Oncogene Fusion , Oncogene Proteins, Fusion/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptor, trkA/genetics , Receptor, trkA/metabolism , Receptor, trkB/genetics , Receptor, trkB/metabolism , Receptor, trkC/genetics , Receptor, trkC/metabolismABSTRACT
Meningioma with cystic component is not a commonly encountered tumor. We report three patients with cystic meningioma histologically confirmed. Tomographic images of these tumours resembled those of a glial or metastatic origin with cystic or necrotic changes and were easily confused. In a 2-year period (1997-1999) in our Department we had three patients with cystic meningioma who account for 5.4% of all patients with meningiomas we have.
