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

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

Research output: Contribution to journalArticlepeer-review


Objectives: 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. Materials and Methods: 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 in vivo. Results: 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; P=0.047), Axin2 (HR:6.883; P=0.014), and Snail abundance (HR:5.663; P=0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; P=0.010), upper (HR:4.332; P=0.005) and lower gingiva (HR:3.545; P=0.012), presence of extranodal extension (HR:9.967; P<0.001), perineural invasion (HR:3.627; P=0.024), and Snail abundance (HR:3.587; P<0.001) had independent impacts on worsened recurrence-free survival. Furthermore, Axin2 knockdown induced decreased Snail expression and attenuated tumorigenesis in the IHOK line. Conclusion: 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.

Original languageEnglish
Article number930988
JournalFrontiers in Oncology
Publication statusPublished - 2022 Jul 7

Bibliographical note

Funding Information:
We thank Ana Luisa Carvalho for datasets 3 and 4, Débora Serrenho for testing the software and Asim Iqbal for reading the manuscript and providing feedback. A.Ö.A. was partially supported by Fundação para a Ciência e a Technologia (FCT) grant SFRH/BD/51264/2010. E.E. was supported by Personalized Health and Related Technologies (PHRT), project number 222, ETH domain. A.F.H. was supported by FCT grant SFRH/BD/51265/2010. The authors would also like to acknowledge the financial support of the European Research Council (ERC) via a Starting Grant to T.K (No. 679175), Fundação Bial (161/10-2010) and (PTDC/SAU-NMC/122035/2010) to I.I., Consejo Nacional de Ciencia y Tecnología (254878) and Programa de Apoyo a Proyectos de Invertigación e Inovación Tecnológica/UNAM (IN207420) to Y.R.C., and the Scientific and Technological Research Council of Turkey (113E603).

Publisher Copyright:
Copyright © 2022 Pei, Han, Kim, Kim, Nam, Kim, Cho, Kim, Cha and Zhang.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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