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Abstract：
Introduction Potentially malignant disorders, like oral lichen planus (OLP) and oral leukoplakia (OL) of several degrees of dysplasia, manifest a significant potential of malignant transformation being a precursor of oral squamous cell carcinoma (OSCC). The role of microvascularization in carcinogenesis is critical; therefore, microvascularization constitutes a major therapeutic target. DAPK-1 constitutes a possible cancer marker, with proven implications in other human cancers, and there isn\'t any study on its vascular endothelial expression in the oral cavity, particularly in oral cancer and oral potentially malignant diseases. The present study aims to investigate the vascular endothelial expression of the DAPK-1 in paraffin-embedded tissue samples of oral leukoplakia, oral squamous cell carcinoma, and oral lichen planus. Materials and methods The study focuses on the immunohistochemical, vascular-endothelial, expression pattern of biomarker DAPK-1 (NBP2-38468, Novus Biologicals, Centennial, CO, US). Tissue samples were obtained from six cases of oral lichen planus (OLP) (3 of reticular and 3 of erosive form), 30 cases of oral leukoplakia (OL) (10 with no dysplasia, 10 with mild dysplasia, and 10 with moderate/severe dysplasia), 22 cases of OSCC (2 well-differentiated, 17 moderately differentiated, and 3 poorly differentiated), as well as 5 cases of normal oral epithelium. The tissue samples were retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, as well as from St Lukas Hospital of Thessaloniki, Greece, from 2004-2019. In accordance with the Research and Ethics Committee guidelines of the Aristotle University, School of Dentistry, and the Helsinki II declaration, the study was conducted. The primary inclusion criteria for the study focused on the presence of sufficient precancerous or cancerous tissue. Conversely, inadequate tissue served as the exclusion criteria. The staining was evaluated exclusively in a quantitative manner. The vascular endothelial staining was evaluated as either positive or negative. If at least one endothelial cell exhibited positive staining, the section was classified as positive. Statistical analysis was carried out using SPSS Statistics v25.0 (IBM Corp., Armonk, NY, US) utilizing Pearson\'s chi-square or Fisher\'s exact test, depending on the sample size, to compare OLP to OL, OLP to OSCC, OLP to normal, OL to OSCC, OL to normal, and OSCC to normal. The significance level was established at 0.05 (p=0.05). Results A prevalence of positive OL cases may be noticed. The comparison between OLP and OL yielded Fisher\'s exact test of p>0.999, OLP and OSCC p=0.389, OLP and normal oral epithelium p>0.999, OL and OSCC p=0.226, OL and normal oral epithelium p>0.999, as well as OSCC and normal oral epithelium p=0.342. Conclusions The role of DAPK in tumorigenesis is already supported by limited literature. However, its implication in the development of OSCC and oral potentially malignant disorders (OPMDs) has yet to be elucidated. Its elevated expression in OL suggests a role in affecting the microenvironment, the vessels, in particular, surrounding oral potentially malignant lesions, possibly assisting their transition into cancer. The evaluation of the vascular-endothelial immunohistochemical profile of DAPK-1 in OL, OLP, and OSCC requires further studies in more tissue samples to illustrate its possible implications.
摘要：
导言潜在的恶性疾病，如口腔扁平苔藓（OLP）和口腔白斑（OL）的几种程度的发育不良，表现出恶性转化的显着潜力，是口腔鳞状细胞癌（OSCC）的前体。微血管形成在癌变中的作用至关重要；因此，微血管形成是主要的治疗靶点。DAPK-1构成了一个可能的癌症标志物，与其他人类癌症的影响，并且没有任何关于其在口腔中的血管内皮表达的研究，特别是在口腔癌和口腔潜在恶性疾病中。本研究旨在探讨口腔白斑石蜡包埋组织中DAPK-1的血管内皮表达,口腔鳞状细胞癌，和口腔扁平苔藓.材料和方法本研究的重点是免疫组织化学，血管内皮，生物标志物DAPK-1的表达模式(NBP2-38468，Novus生物制品，百周年纪念,CO,美国)。从6例口腔扁平苔藓（OLP）（3例网状和3例糜烂形式）获得组织样本，口腔白斑（OL）30例（10例无发育不良，10患有轻度发育不良，和10中度/重度发育不良)，22例OSCC（2例高分化，17中等分化，和3分化差)，以及5例正常口腔上皮。从口腔医学/病理学系的档案中检索组织样本，牙科学院,塞萨洛尼基亚里士多德大学,以及塞萨洛尼基的圣卢卡斯医院，希腊,从2004年到2019年。根据亚里士多德大学研究与伦理委员会的指导方针，牙科学院,和赫尔辛基二世宣言，进行了这项研究。该研究的主要纳入标准集中在是否存在足够的癌前组织或癌组织。相反，组织不足作为排除标准。以定量方式专门评价染色。血管内皮染色评价为阳性或阴性。如果至少一个内皮细胞显示阳性染色，该部分被归类为阳性。使用SPSSStatisticsv25.0(IBMCorp.,Armonk,NY,美国)利用皮尔逊卡方或费舍尔精确检验，根据样本大小，要将OLP与OL进行比较，OLP到OSCC,OLP到正常，从OL到OSCC,OL到正常，和OSCC正常。显著性水平建立在0.05(p=0.05)。结果可以注意到阳性OL病例的患病率。OLP和OL之间的比较得出Fisher精确检验p>0.999，OLP和OSCCp=0.389，OLP和正常口腔上皮p>0.999，OL和OSCCp=0.226，OL和正常口腔上皮p>0.999，以及OSCC和正常口腔上皮p=0.342。结论DAPK在肿瘤发生中的作用已得到有限文献的支持。然而,其在OSCC和口腔潜在恶性疾病（OPMDs）发展中的意义尚未阐明。它在OL中的表达升高表明在影响微环境中起作用，船只,特别是,周围的口腔潜在恶性病变，可能帮助他们过渡到癌症。在OL中DAPK-1的血管内皮免疫组织化学谱的评估，OLP,OSCC需要在更多的组织样本中进行进一步的研究，以说明其可能的含义。
