Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer

Abstract

Background:Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding.Methods:Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections.Results:Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26–3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation.Conclusions:Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal metastasis and recurrence

“…However, on multivariate analysis higher tumor bud scores were also associated with recurrence (hazard ratio 1.60), but the P-value approached, but did not meet significance (P=0.08). Our results agree with previous research [18,25,26], supporting the hypothesis that increased tumor budding in GAC portends an increased risk of adverse outcomes, including lymph node involvement and recurrence. However, more studies are needed to better analyze the value of tumor budding in gastric carcinoma.…”

“…Tanaka et al also found that a high level of tumor budding was associated with increasing T-stage, N-stage, lymphatic involvement, and metastasis on univariate analysis, but did not maintain significance in multivariate analysis combined with TNM staging [25]. Of note, similar to our methodology, both of these investigators excluded the signet ring and undifferentiated tumors from their analysis.…”

“…Similar studies have also shown a similar relationship in adenocarcinomas of the ampulla [21], esophagus [22,23], and pancreas [24]. However, very little research has been performed evaluating tumor budding in GAC [18,25,26]. The aim of this study is to further evaluate the prognostic value that tumor budding may have in GAC.…”

Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer

“…In addition, various critical molecular events that regulate tumour proliferation, adhesion/migration, and angiogenesis occur in the ITF (Bankfalvi and Piffko, 2000; Rowe and Weiss, 2009; Sharma et al , 2013). Accordingly, the ITF is mainly responsible for the clinical behaviour of the tumour (Khanh do et al , 2011; Tanaka et al , 2014). However, it is not clear whether the presence of CSCs at the ITF has clinical significance.…”

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

“…Yet in recent studies, increasing evidence has revealed that both BDNF and its receptor TrkB are overexpressed in a variety of malignances, including head and neck squamous cell carcinoma (21), breast cancer (6), colorectal cancer (7), hepatocellular cancer (22) and gastric cancer (23). Overexpression of these two markers in malignant tumors is consistently associated with a more aggressive behavior and poor prognosis (6,7,(21)(22)(23). Furthermore, our previous studies demonstrated that overexpression of BDNF/TrkB is significantly correlated with clinical stage, perineural or vascular invasion, distant metastasis, and poor prognosis of SACC (8).…”