Hsieh Pi-Chuan, Chen Yuk-Kwan, Tsai Kun-Bow, Shieh Tien-Yu, Chang Yong-Yuan, Chang Jan-Gowth, Wu Hsin-Lung, Lin Sheng-Fung
Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Feb;109(2):257-67. doi: 10.1016/j.tripleo.2009.08.014. Epub 2009 Nov 17.
BUBR1 is one of the key components of the spindle assembly checkpoint (SAC) machinery and is activated in response to kinetochore tension. Defects in the SAC contribute to an increased rate of aneuploidization during tumorigenesis. The aim of the present study was to examine the immunohistochemical expression of BUBR1 protein for human oral squamous cell carcinogenesis.
A total of 120 samples of squamous cell carcinoma (SCC, n = 43) and 5 types of potentially malignant disorders (PMDs: oral epithelial dysplasia, n = 11; hyperkeratosis/epithelial hyperplasia, n = 20; lichen planus, n = 16; submucous fibrosis, n = 19; and verrucous hyperplasia, n = 11) of human oral mucosa (1991-2001) from our institution were retrieved and immunohistochemical staining were performed. Normal oral mucosa (n = 9) and fibrous hyperplasia (n = 9) from patients without the aforementioned oral habits were also included in the study.
BUBR1 staining was detected at the basal and suprabasal layers in 75 (97.4%) of 77 samples of PMD and 43 (100%) of 43 samples of SCC of oral mucosa but was absent in all samples of normal oral mucosa (n = 9) and fibrous hyperplasia (n = 9). BUBR1 expression of various types of PMD and SCC of oral mucosa was significantly overexpressed as compared respectively with normal mucosa (P < .001) and fibrous hyperplasia (P < .001). Moreover, the expression of oral SCC was significantly higher as compared respectively with the 5 types of oral PMD; on the other hand, BUBR1 expression of verrucous hyperplasia was significantly higher than that of the other 4 types of PMD of oral mucosa (P < .001).
Our results may interpret that BUBR1 protein is suggested to be one of the contributing factors involved in the pathogenesis of oral SCC. These also hypothesize that BUBR1 protein is a putative biomarker for human oral squamous cell carcinogenesis.
BUBR1是纺锤体组装检查点（SAC）机制的关键组成部分之一，可响应动粒张力而被激活。SAC缺陷会导致肿瘤发生过程中非整倍体化率增加。本研究旨在检测BUBR1蛋白在人类口腔鳞状细胞癌发生过程中的免疫组化表达。
从我们机构收集了1991年至2001年的120份人类口腔黏膜样本，包括鳞状细胞癌（SCC，n = 43）以及5种潜在恶性疾病（PMD：口腔上皮发育异常，n = 11；角化过度/上皮增生，n = 20；扁平苔藓，n = 16；黏膜下纤维化，n = 19；疣状增生，n = 11），并进行免疫组化染色。研究还纳入了无上述口腔习惯患者的正常口腔黏膜（n = 9）和纤维增生（n = 9）样本。
在77份PMD样本中的75份（97.4%）以及43份口腔黏膜SCC样本中的43份（100%）的基底层和基底上层检测到BUBR1染色，但在所有正常口腔黏膜样本（n = 9）和纤维增生样本（n = 9）中均未检测到。与正常黏膜（P <.001）和纤维增生（P <.001）相比，各种类型的口腔黏膜PMD和SCC中BUBR1的表达均显著上调。此外，与5种口腔PMD相比，口腔SCC的表达分别显著更高；另一方面，疣状增生中BUBR1的表达显著高于其他4种口腔黏膜PMD（P <.001）。
我们的结果可能表明，BUBR1蛋白被认为是参与口腔SCC发病机制中的因素之一。这些结果还推测，BUBR1蛋白是人类口腔鳞状细胞癌发生的一种假定生物标志物。
