Ryoji Yoshida

Background: Small mothers against decapentaplegic homologue 4 (SMAD4) plays an important role in transforming growth factor (TGF)‐β signaling and is associated with various cancers. However, little is known about SMAD4 expression in oral squamous cell carcinoma (OSCC). Aim: To investigate the clinical and biological significance of SMAD4 expression in OSCC. Methods and Results: Immunohistochemical analysis was performed to detect SMAD4 expression in 90 OSCC specimens obtained from patients who underwent preoperative chemoradiotherapy and surgery (phase II study). We also investigated the correlation between SMAD4 expression and various clinicopathological features. In vitro experiments were performed to assess the effects of SMAD4 expression on chemosensitivity and changes in apoptosis‐related molecules. Notably, low SMAD4 expression was significantly correlated with an increased risk of lymph node metastasis, poor response to chemoradiotherapy, and adverse prognosis in patients with OSCC who underwent preoperative 5‐FU‐based chemoradiotherapy. Additionally, SMAD4 downregulation in OSCC cells decreased sensitivity to cisplatin and 5‐fluorouracil and was associated with an increase in cIAP2 expression. Conclusion: The reduced expression of SMAD4 has been linked to both chemotherapy resistance and prognosis in OSCC. However, it may not function as an independent prognostic biomarker. Further research is necessary to determine whether these findings can be generalized to the broader OSCC population.

Background: Squamous cell carcinoma of the buccal mucosa (SCCBM) is a prevalent malignancy of the oral cavity with high morbidity and mortality rates. The pterygomandibular raphe (PMR) connects the oral cavity, pharynx, and masticator space, serving as a key anatomical landmark during surgical resection. However, PMR invasion into SCCBM remains poorly understood. This study assessed the prognostic significance of PMR invasion in patients with resectable SCCBM. Methods: The study included 82 patients with SCCBM, excluding those with T4b, who underwent radical resection at Kumamoto University Hospital between 2000 and 2017. Patients were categorized into three groups based on PMR invasion patterns: non-contact, contact, and invasion. The relationship between PMR invasion and clinicopathological characteristics was analyzed using the Fisher’s exact test. The Kaplan–Meier method, log-rank test, and propensity score-matched analyses were used for survival analysis. Results: Contact or invasion into the PMR was significantly associated with advanced clinical T and N stages, clinical stage, endophytic growth pattern, high-grade invasion pattern, and poor tumor differentiation. Patients with PMR invasion had a higher proportion of recurrences in the buccal subcutaneous, mandibular, and masticator spaces. Univariate analysis indicated that contact- or invasion-type PMR invasion predicted worse overall survival (OS). The impact of PMR invasion on OS was confirmed using a propensity score-matched analysis. Conclusion: This study revealed that PMR invasion is a potential novel grading and prognostic factor for resectable SCCBM, with significance in planning the extent of SCCBM resection.