AUTHOR=Pei Meiling , Han Dawool , Kim Ki-Yeol , Kim Dong Wook , Nam Woong , Kim Hyung Jun , Cho Eunae Sandra , Kim Hyun Sil , Cha In-Ho , Zhang Xianglan 

TITLE=Risk Factors of Microscopically Tumor-Free Surgical Margins for Recurrence and Survival of Oral Squamous Cell Carcinoma Patients

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.930988

DOI=10.3389/fonc.2022.930988

ISSN=2234-943X

ABSTRACT=<sec><title>Objectives</title><p>The concept of adequate surgical margins remains controversial in oral squamous cell carcinoma (OSCC) surgery. This study aimed to identify surgical margin-related indicators that might impact recurrence and survival of OSCC patients.</p></sec><sec><title>Materials and Methods</title><p>Histopathological examination was performed using hematoxylin-eosin-stained surgical margin tissue sections in 235 OSCC patients. Axin2 and Snail expression at the surgical margin was detected by immunohistochemistry. The impact of the Axin2-Snail cascade on tumorigenesis of the immortalized human oral keratinocyte (IHOK) line was investigated <italic>in vivo</italic>.</p></sec><sec><title>Results</title><p>The width and dysplasia of surgical margins were not significantly associated with the outcome of OSCC patients. In a multivariate analysis using variable clinicopathologic factors and with Axin2 and Snail expression as cofactors, higher age (hazard ratio [HR]:1.050; <italic>P</italic>=0.047), Axin2 (HR:6.883; <italic>P</italic>=0.014), and Snail abundance (HR:5.663; <italic>P</italic>=0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; <italic>P</italic>=0.010), upper (HR:4.332; <italic>P</italic>=0.005) and lower gingiva (HR:3.545; <italic>P</italic>=0.012), presence of extranodal extension (HR:9.967; <italic>P</italic>&lt;0.001), perineural invasion (HR:3.627; <italic>P</italic>=0.024), and Snail abundance (HR:3.587; <italic>P</italic>&lt;0.001) had independent impacts on worsened recurrence-free survival. Furthermore, Axin2 knockdown induced decreased Snail expression and attenuated tumorigenesis in the IHOK line.</p></sec><sec><title>Conclusion</title><p>Histopathological examination of surgical margins may not be reliable to predict OSCC patient outcome. Molecular analysis may provide a more accurate risk assessment of surgical margins in OSCC. In particular, Axin2 and Snail are potential predictive biomarkers for the risk assessment of surgical margins in OSCC.</p></sec>