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Updated: Sep 5, 2025

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
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Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer.

Ligia B Schmitd1, Cindy Perez-Pacheco1, Emily L Bellile2

  • 1Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 12, 2022
PubMed
Summary
This summary is machine-generated.

Perineural invasion (PNI) in oral cancer predicts poor survival. Nerve-tumor distance, not just PNI presence, is crucial for prognosis, suggesting new diagnostic criteria are needed.

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Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Pathology

Background:

  • Perineural invasion (PNI) is common in oral squamous cell carcinomas and linked to poor survival.
  • Current diagnostic criteria for PNI vary, and its prognostic significance as an independent predictor is not fully established.

Purpose of the Study:

  • To investigate the spatial and transcriptomic profiles of nerves in relation to oral squamous cell carcinoma.
  • To clarify the role of PNI and nerve-tumor proximity in patient prognosis.

Main Methods:

  • Analysis of 142 oral squamous cell carcinoma patient tissue sections, stained for S100 and cytokeratin.
  • Assessment of nerve diameter and nerve-tumor distance in tumor bulk and margin.
  • Spatial transcriptomic analysis using NanoString GeoMx Digital Spatial Profiler.

Main Results:

  • PNI is an independent predictor of poor prognosis, even in patients with metastasis-free lymph nodes.
  • Close nerve-tumor distance correlates with poor outcomes, irrespective of current PNI diagnostic criteria.
  • Transcriptomic analysis revealed cancer-induced nerve stress and growth responses that correlate with clinical outcomes.

Conclusions:

  • Nerve-tumor proximity is a critical factor in oral cancer progression and patient survival.
  • Current subjective criteria for PNI diagnosis should be re-evaluated.
  • This study provides a foundation for reclassifying PNI based on objective nerve-tumor distance and associated molecular changes.