Kudo Itsuhiro, Esumi Mariko, Kusumi Yoshiaki, Furusaka Tohru, Oshima Takeshi
Department of Pathology, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Oncol Lett. 2017 Oct;14(4):4633-4640. doi: 10.3892/ol.2017.6751. Epub 2017 Aug 14.
It has been demonstrated that tumor protein p53 () mutation in maxillary squamous cell carcinoma, is more treatment-resistant compared with the carcinoma without mutation. However, the association between mutation and treatment resistance remains unclear. As a first step in understanding the biological differences between tumors with and without mutation, a comprehensive gene expression analysis of maxillary squamous cell carcinoma with or without mutation was performed. A total of 42 genes were identified to be differentially expressed by >4-fold. Quantification of their mRNA using quantitative polymerase chain reaction indicated 18 genes with high expression and three genes with low expression in mutated tumors vs. wild-type tumors. The 18 genes included eight cell adhesion (, , and B) and four cell growth inhibition (, , and 3) genes. Among these genes, , , and , whose expression was markedly increased, also demonstrated high protein expression in immunohistochemical staining of mutated tumors. The mutated tumors demonstrated high nuclear staining of the TP53 protein only in tumor cells at the tumor margins adjacent to the stroma, whereas the tumor interior was negative for TP53. However, all tumor cells of wild-type tumors exhibited positive nuclear staining for the TP53 protein. The combined findings suggest that mutated tumors possess a phenotype opposite to that associated with cancer progression and malignant transformation, and exhibit tumor cell heterogeneity between the tumor interior and margins.
已经证明，上颌鳞状细胞癌中的肿瘤蛋白p53（）突变与无该突变的癌相比，对治疗更具抗性。然而，该突变与治疗抗性之间的关联仍不清楚。作为了解有或无该突变的肿瘤之间生物学差异的第一步，对有或无该突变的上颌鳞状细胞癌进行了全面的基因表达分析。共鉴定出42个基因的差异表达超过4倍。使用定量聚合酶链反应对其mRNA进行定量分析表明，与野生型肿瘤相比，该突变肿瘤中有18个基因高表达，3个基因低表达。这18个基因包括8个细胞黏附（、和B）和4个细胞生长抑制（、、和3）基因。在这些基因中，表达明显增加的、和，在该突变肿瘤的免疫组织化学染色中也显示出高蛋白表达。该突变肿瘤仅在与基质相邻的肿瘤边缘的肿瘤细胞中显示TP53蛋白的高核染色，而肿瘤内部TP53呈阴性。然而，野生型肿瘤的所有肿瘤细胞均显示TP53蛋白的阳性核染色。综合研究结果表明，该突变肿瘤具有与癌症进展和恶性转化相关的相反表型，并在肿瘤内部和边缘表现出肿瘤细胞异质性。
