Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis staging system

The aim of this study was to determine the prognostic value of perineural invasion (PNI) in patients with gastric cancer who underwent curative resection. We retrospectively analyzed 518 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. Patients with PNI had a significantly larger tumors (a parts per thousand yen5.0 cm), lymphatic venous invasion (positive), deeper tumor invasion (T4), more number of lymph node metastases (N3), and higher tumor stage (III). Regarding survival, multivariate analysis showed that PNI emerged as an independent prognostic factor for survival (hazard ratio (HR) = 1.901, P < 0.001). We incorporated the PNI into the 7th edition tumor-node-metastasis (TNM) staging system. Comparing with the 7th edition staging system, the redefinition of TPNI stage had higher -2loglikelihood value (-2loglikelihood = 3,492.259) and lower HR and 95 % confidence interval (CI) (HR = 1.955, 95 % CI = 1.630-2.343); redefinition of N-PNI and TNMIIIPNI stage both had lower -2loglikelihood value (-2loglikelihood = 3,306.608; -2loglikelihood = 2,535.151) and higher HR and 95 % CI (HR = 1.879, 95 % CI = 1.720-2.053; HR = 2.268, 95 % CI = 1.900-2.707), which represented the optimum prognostic stratification, together with better homogeneity, discriminatory ability. Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer and it should be incorporated into TNM staging.