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
Department of Dermatology, Yonsei University College of Dentistry, Seoul, South Korea.
Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, South Korea.
Front Oncol. 2022 Jul 7;12:930988. doi: 10.3389/fonc.2022.930988. eCollection 2022.
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.
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 .
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.
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.
在口腔鳞状细胞癌（OSCC）手术中，足够手术切缘的概念仍存在争议。本研究旨在确定可能影响OSCC患者复发和生存的手术切缘相关指标。
对235例OSCC患者手术切缘组织切片进行苏木精-伊红染色，进行组织病理学检查。采用免疫组织化学法检测手术切缘处Axin2和Snail的表达。研究Axin2-Snail级联反应对永生化人口腔角质形成细胞（IHOK）系肿瘤发生的影响。
手术切缘的宽度和发育异常与OSCC患者的预后无显著相关性。在使用可变临床病理因素并以Axin2和Snail表达作为辅助因素的多因素分析中，年龄较大（风险比[HR]：1.050；P = 0.047）、Axin2（HR：6.883；P = 0.014）和Snail丰度（HR：5.663；P = 0.009）对总生存期恶化有独立影响。同样，磨牙后三角区病变部位（HR：4.077；P = 0.010）、上牙龈（HR：4.332；P = 0.005）和下牙龈（HR：3.545；P = 0.012）、结外扩展的存在（HR：9.967；P < 0.001）、神经周围侵犯（HR：3.627；P = 0.024）和Snail丰度（HR：3.587；P < 0.001）对无复发生存期恶化有独立影响。此外，Axin2基因敲低导致IHOK系中Snail表达降低并减弱肿瘤发生。
手术切缘的组织病理学检查可能无法可靠地预测OSCC患者的预后。分子分析可能为OSCC手术切缘提供更准确的风险评估。特别是，Axin2和Snail是OSCC手术切缘风险评估的潜在预测生物标志物。
