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Updated: Aug 5, 2026
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Nodal burden modifies the prognostic significance of perineural invasion in stage I-III gastric cancer
Qi Wang1,2,3, Hongxue Meng4, Shizheng Xiong1,2,3
1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Background:
Perineural invasion (PNI) is an established adverse prognostic factor in gastric cancer, but whether its prognostic effect varies with nodal burden and first metastatic site remains unclear.
Methods:
We retrospectively analyzed 12,898 patients with stage I-III gastric cancer who underwent curative-intent R0 gastrectomy at Fudan University Shanghai Cancer Center between 2000 and 2022. Multivariable Cox models with a pre-specified PNI-by-positive-node interaction estimated associations with overall survival (OS) and progression-free survival (PFS). First distant metastatic site was evaluated using Fine-Gray and Firth logistic site-contrast models. The PNI-nodal-burden association was assessed in an independent pathology cohort and the ACRG cohort.
Results:
Each additional positive lymph node attenuated the PNI-associated hazard ratio for OS (interaction HR, 0.976) and PFS (interaction HR, 0.977; both interaction P < 0.001). PNI was independently associated with poorer OS (HR, 1.38; 95% CI 1.20-1.59) and PFS (HR, 1.32; 95% CI 1.15-1.51) in N0-N1 disease, but the associations were attenuated in N2-N3 disease (OS: HR, 1.12; 95% CI 1.00-1.24; PFS: HR, 1.09; 95% CI 0.99-1.21). Among N0-N1 patients with pT3-pT4 disease and liver-only or peritoneal-only first metastasis, PNI was associated with peritoneal rather than hepatic dissemination (OR, 3.87; 95% CI 1.54-10.63).
Conclusions:
The prognostic association of PNI was modified by nodal burden and was most evident in N0-N1 gastric cancer. These site-specific findings support prospective evaluation of PNI-informed, peritoneum-directed surveillance.
