Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma

Abstract

Background Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor–Node–Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. Methods About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni‐/multifocal and as intra‐/peritumoral. Disease‐Specific and Relapse‐Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. Results Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph–node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p‐value = 0.008). Moreover, patients exhibiting both multifocal intra‐ and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p‐value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. Conclusions Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

Prognostic Value of Perineural Invasion in Oral Tongue Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

“…PNI is associated with the depth of invasion of OTSCC (22) and cervical lymph node involvement and might suggest consideration for elective neck dissection (23), even in stage 1 and 2 diseases (24). A significant number of recently published research has outlined the contribution of PNI to clinical outcomes in OTSCC (10,(19)(20)(21)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Some authors advocate incorporating PNI in the staging systems for OTSCC (34).…”

Progression Risk Score Estimation Based on Immunostaining Data in Oral Cancer Using Unsupervised Hierarchical Clustering Analysis: A Retrospective Study in Taiwan

“…The PRS can recognize the interaction between factors by considering associations within a protein cluster and is available in the extended analysis with clinical parameters in typical survival analysis approaches. The prognostic role of clinical parameters in oral cancer has been previously reported and indicated that oral cancer patients with a poorly differentiated grade, LVI, PNI, presence of tumor in the surgical margin, lymph node invasion, ENE, lymph node invasion, and the advanced pathological stage could obtain a poor survival outcome [22,23]. Moreover, the expression of four individual proteins, such as phosphoMet, was also altered in different clinical characteristics subgroups, including age and stage [24].…”

Worst Pattern of Perineural Invasion Redefines the Spatial Localization of Nerves in Oral Squamous Cell Carcinoma

“…However, in 200 patients with oral tongue SCC, Caponio et al. presented that intratumoral PNI combined with tumor grading and WPOI could successfully predict lymph-node metastasis and advocated integrating PNI in the 8th edition of the AJCC Cancer staging system ( 30 ).…”

“…Although the proportion of lymphocyte subsets did not significantly change with different WPNI scores (Figure 5E), the absolute number of total T cells (CD3 + ), inhibitory T cells (CD3 + CD8 + ), and B cells (CD19 + ) were all significantly decreased in WPNI 3 patients (p = 0.01, p = 0.01, and p = 0.008, respectively; Figure 5F), further suggesting a possible imbalance in immune response. (30).…”