Article
Neural invasion is not a prognostic factor in colon cancer due to missing neuro-cancer cell affinity
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Published: | May 20, 2011 |
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Introduction: Neural invasion (NI) is a histopathological feature of colon cancer (CC) which still has little clinical impact. This may be due to the low prevalence of NI in CC compared to other gastrointestinal malignancies like in pancreatic adenocarcinoma (PCa). The aim of this study was to perform a comprehensive morphological and functional characterization of NI in CC and to assess its actual role in colon cancer biology.
Materials and methods: NI was characterized in H&E-stained tissue sections of 673 patients with CC. The exact localization and the severity of NI was determined and related to patient’s prognosis and survival. To determine a potential affinity between CC cell lines (HT29, HCT-116) and neurons, a recently established 3D- in-vitro neural migration assay was utilized. Here cancer cells were co-cultivated with isolated dorsal root ganglia (DRG) of newborn rats and the migratory behaviour of CC cells towards the neural structures was compared to that of the PCa cell line T3M4 via live cell imaging analysis.
Results: NI was detected in 210 of 673 patients (31.2 %). Although increasing NI severity scores were associated with a significantly poorer survival, multivariate analysis including gender, age, pTNM stage, tumor grading, lymphatic invasion, CEA-level, resection status and tumor location did not reveal NI as an independent prognostic factor in CC. In the 3D migration assay, CC cells did not demonstrate any neurite-targeted migration behavior, whereas T3M4 cells revealed a high selective targeted and fast migration towards the isolated DRG.
Conclusion: NI is not an independent prognostic factor in colon cancer. The lack of a considerable biological affinity between CC cells and neurons and the predominantly intraperitoneal localization of colon segments may explain the low prevalence and impact of NI in colon cancer compared to pancreatic cancer.