Abstract

Background: Neural invasion of cancer cells (NI) seems to have an important clinical impact in rectal adenocarcinoma (RC). However, a unique definition of neural invasion is still missing. Therefore, the aim of this study was to provide a consistent definition of neural invasion in RC and to establish a novel NI severity score. Furthermore, we aimed to assess the potential prognostic value of NI, depending on neoadjuvant treatment. Patients and Methods: NI was characterized in haematoxylinand eosin-stained sections of the primary tumor (uT3), mesorectal fat, adjacent normal tissue and all resected lymph nodes from paraffin-embedded specimens of 296 patients with rectal cancer (139 patients with primary resection, 157 patients with neoadjuvant radiochemotherapy/nRCTx; 45Gy/5-FU). To further classify NI in rectal cancer, the severity and localisation of neural invasion was determined and related to patients‚ prognosis and survival. Results: NI was detected in 44 of 139 patients (32 %) with primary resection while in patients with pre-operative radiochemotherapy, NI was found in 29 of 157 patients (20 %, p = 0.026). The prevalence of NI in the main tumor mass within the primary resection group was 6.4 %, whereas it was completely absent in the nRCTx group. Moreover, increasing NI severity was associated with a significantly poorer survival in both groups. Multivariate analysis including TNM-stage, grading and CEA value revealed NI as an independent prognostic factor among primarily resected and nRCTx patients. Conclusion: Systematic scoring of NI in rectal cancer demonstrates that severe NI exerts a prominent influence on patient survival. Furthermore, nRCTx may have an impact to decrease NI in the main tumor mass and reduce the absolute number of afflicted nerves. NI is an independent prognostic factor among patients with rectal cancer receiving nRCTX and should therefore be considered in the therapy regime.