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

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jul 25

PMID 35875099

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 .

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; =0.047), Axin2 (HR:6.883; =0.014), and Snail abundance (HR:5.663; =0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; =0.010), upper (HR:4.332; =0.005) and lower gingiva (HR:3.545; =0.012), presence of extranodal extension (HR:9.967; <0.001), perineural invasion (HR:3.627; =0.024), and Snail abundance (HR:3.587; <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.

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References

Kunstfeld R, Wickenhauser G, Michaelis U, Teifel M, Umek W, Naujoks K . Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a "humanized" SCID mouse model. J Invest Dermatol. 2003; 120(3):476-82. DOI: 10.1046/j.1523-1747.2003.12057.x. View

Pannone G, Santoro A, Papagerakis S, Lo Muzio L, De Rosa G, Bufo P . The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview. Infect Agent Cancer. 2011; 6:4. PMC: 3072321. DOI: 10.1186/1750-9378-6-4. View

Singh A, Mair M, Singhvi H, Ramalingam N, Bal M, Lamba K . Incidence and impact of dysplasia at final resection margins in cancers of the oral cavity. Acta Otolaryngol. 2020; 140(11):963-969. DOI: 10.1080/00016489.2020.1785642. View

Posner M, Hershock D, Blajman C, Mickiewicz E, Winquist E, Gorbounova V . Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007; 357(17):1705-15. DOI: 10.1056/NEJMoa070956. View

Chiou W, Lin H, Hsu F, Lee M, Ho H, Su Y . Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence. Radiat Oncol. 2010; 5:79. PMC: 2946296. DOI: 10.1186/1748-717X-5-79. View

Pereira Sorroche B, Talukdar F, Lima S, Melendez M, de Carvalho A, de Almeida G . DNA Methylation Markers from Negative Surgical Margins Can Predict Recurrence of Oral Squamous Cell Carcinoma. Cancers (Basel). 2021; 13(12). PMC: 8230600. DOI: 10.3390/cancers13122915. View

Scully C, Porter S . ABC of oral health. Oral cancer. BMJ. 2000; 321(7253):97-100. PMC: 1127769. DOI: 10.1136/bmj.321.7253.97. View

Smith B, Burton L, Henderson V, Randle D, Morton D, Smith B . Snail promotes epithelial mesenchymal transition in breast cancer cells in part via activation of nuclear ERK2. PLoS One. 2014; 9(8):e104987. PMC: 4133359. DOI: 10.1371/journal.pone.0104987. View

Smits R, Koljenovic S, Hardillo J, Ten Hove I, Meeuwis C, Sewnaik A . Resection margins in oral cancer surgery: Room for improvement. Head Neck. 2015; 38 Suppl 1:E2197-203. DOI: 10.1002/hed.24075. View

10.

Puisieux A, Brabletz T, Caramel J . Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol. 2014; 16(6):488-94. DOI: 10.1038/ncb2976. View

11.

Ow T, Myers J . Current management of advanced resectable oral cavity squamous cell carcinoma. Clin Exp Otorhinolaryngol. 2011; 4(1):1-10. PMC: 3062220. DOI: 10.3342/ceo.2011.4.1.1. View

12.

Meier J, Oliver D, Varvares M . Surgical margin determination in head and neck oncology: current clinical practice. The results of an International American Head and Neck Society Member Survey. Head Neck. 2005; 27(11):952-8. DOI: 10.1002/hed.20269. View

13.

In Yook J, Li X, Ota I, Hu C, Kim H, Kim N . A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006; 8(12):1398-406. DOI: 10.1038/ncb1508. View

14.

Liu W, Bao Z, Shi L, Tang G, Zhou Z . Malignant transformation of oral epithelial dysplasia: clinicopathological risk factors and outcome analysis in a retrospective cohort of 138 cases. Histopathology. 2011; 59(4):733-40. DOI: 10.1111/j.1365-2559.2011.03938.x. View

15.

Wong L, McMahon J, DeVine J, McLellan D, Thompson E, Farrow A . Influence of close resection margins on local recurrence and disease-specific survival in oral and oropharyngeal carcinoma. Br J Oral Maxillofac Surg. 2011; 50(2):102-8. DOI: 10.1016/j.bjoms.2011.05.008. View

16.

Chen T, Wang C, Ko J, Yang T, Lou P . The impact of pathologic close margin on the survival of patients with early stage oral squamous cell carcinoma. Oral Oncol. 2012; 48(7):623-8. DOI: 10.1016/j.oraloncology.2012.01.015. View

17.

Kujan O, Oliver R, Khattab A, Roberts S, Thakker N, Sloan P . Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006; 42(10):987-93. DOI: 10.1016/j.oraloncology.2005.12.014. View

18.

Yang X, Han M, Han H, Wang B, Li S, Zhang Z . Silencing Snail suppresses tumor cell proliferation and invasion by reversing epithelial-to-mesenchymal transition and arresting G2/M phase in non-small cell lung cancer. Int J Oncol. 2017; 50(4):1251-1260. DOI: 10.3892/ijo.2017.3888. View

19.

Jayanthi P, Varun B, Selvaraj J . Epithelial-mesenchymal transition in oral squamous cell carcinoma: An insight into molecular mechanisms and clinical implications. J Oral Maxillofac Pathol. 2020; 24(1):189. PMC: 7269282. DOI: 10.4103/jomfp.JOMFP_334_19. View

20.

Zhang X, Han S, Han H, Ryu M, Kim K, Choi E . Risk prediction for malignant conversion of oral epithelial dysplasia by hypoxia related protein expression. Pathology. 2013; 45(5):478-83. DOI: 10.1097/PAT.0b013e3283632624. View