Objectives: Perineural invasion (PNI) portends poor survival in oral cancer, leading to selection of aggressive treatment. PNI is defined as cancer within or surrounding 33% of the nerve, but current evidence shows that nerve-tumor crosstalk happens prior to contact. Our goal was to comprehensively analyze nerves in oral cancer to investigate correlations with clinical outcome. Methods: Biopsy specimens from 71 patients with oral cavity squamous cell carcinoma (OSCC) (41 males, 30 females, mean age 60.2) were sectioned and stained with hematoxylin-eosin (H&E), and immunohistochemical stains (cytokeratin, S-100, Tuj1 and GAP43 antibodies or IgG as a negative control). Scanned slides were digitally analyzed. Tumor and nerve characteristics were assessed by IHC. GAP43 expression of each nerve was compared to Tuj1. Results: PNI was scored by H&E alone and by H&E+IHC; detection was 22.5% with H&E alone and increased to 33.8% with concurrent IHC. PNI associated with worse overall survival (OS) (p=0.098) and among patients without clinical nodal metastasis PNI was associated with poor survival (p=0.057). Smaller nerve-tumor distances adversely impacted survival (Adjusted Cox modeling, HR0.63, 95%CI, p=0.003). Nerves closer to the tumor also expressed more GAP43, suggesting an increased axonal outgrowth in these areas. Conclusions: Our findings from a small group of patients suggest that PNI is related to poor outcome in OSCC patients and that adding IHC to the analysis increased PNI detection. Also, small nerve-tumor distances associated with worse outcome, consistent with previous studies showing tumor-nerve interactions before physical contact. These novel findings could potentially redefine criteria for neural invasion in clinical specimens.
AADR/CADR Annual Meeting
2018 AADR/CADR Annual Meeting (Fort Lauderdale, Florida) Fort Lauderdale, Florida
2018 0059 Oral Medicine & Pathology Research
Schmitd, Ligia
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Taylor, Jeremy
( University of Michigan School of Public Health
, Ann Arbor
, Michigan
, United States
)
D'silva, Nisha
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Beesley, Lauren
( University of Michigan School of Public Health
, Ann Arbor
, Michigan
, United States
)
Russo, Nickole
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Bellile, Emily
( University of Michigan School of Public Health
, Ann Arbor
, Michigan
, United States
)
Inglehart, Ronald
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Gordon, Christopher
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Liu, Min
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Pierchala, Brian
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
Wolf, Gregory
( University of Michigan
, Ann Arbor
, Michigan
, United States
)
This work was supported by grants from NIH/NIDCR DE024384 and DE027551
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