Cytoplasmic TrkA Expression as a Screen for Detecting NTRK1 Fusions in Colorectal Cancer

Autor: Geun Am Song, Hong-Jae Jo, Won-Young Park, Sojeong Lee, Do Youn Park, Ahrong Kim, Chae Hwa Kwon, Y K Kim, Yuri Choi, Yeo-Jin Won
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Translational Oncology, Vol 11, Iss 3, Pp 764-770 (2018)
Translational Oncology
ISSN: 1936-5233
Popis: NTRK1 gene fusions, the targets of multikinase inhibitors, are promising therapeutic targets for colorectal cancer (CRC). However, screening methods for detecting NTRK1 gene fusions in CRC tissues have not been reported. In this study, we investigated the potential use of immunohistochemistry (IHC) for detecting NTRK1 gene fusions. We performed and compared IHC with fluorescence in situ hybridization (FISH) in 80 CRC patients. TrkA immunostaining was observed to be both membranous and cytoplasmic and was scored semiquantitatively using staining intensity and proportions. The tumors were observed to be NTRK1 gene fusion-positive when ≥20 out of 100 nuclei in FISH. A significant correlation between the IHC and FISH results for determination of the NTRK1 gene fusions was observed. We measured the cytoplasmic TrkA expression, which showed an area under the receiver operating characteristic (ROC) curve of 0.926 (range: 0.864-0.987, 95% CI, P = .001). By choosing 4.5 (sum of the intensity and proportion scores of cytoplasmic TrkA expression) as the cut-off value for the positive and negative NTRK1 gene fusion groups, the sensitivity and specificity for predicting lymph node metastasis were 100 and 83.8%, respectively (P = .001). Specifically, high cytoplasmic TrkA expression (sum of intensity and proportion scores >4) was associated with the presence of NTRK1 gene fusions (P
Databáze: OpenAIRE