Amaral Fabrício Rezende, Bernardes Vanessa Fátima, Duarte Alessandra Pires, Pereira Núbia Braga, Vasconcelos Anilton César, Gomez Ricardo Santiago, Gomes Carolina Cavaliéri
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Tumour Biol. 2011 Oct;32(5):997-1003. doi: 10.1007/s13277-011-0201-6. Epub 2011 Jun 25.
Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) of the jaws are characterized by multinucleated osteoclast-like giant cells in a background of mononuclear cells. While mononuclear cells retain proliferative activity in both lesions, giant cells are Ki-67 negative. This observation raised the theory that giant cells are formed by cytoplasmic fusion of mononuclear cells, and also that these lesions are of reactive nature. As the giant cells are not proliferating in CGCL and PGCL, apoptosis of such cells should be investigated. We investigated the transcription of BAX and BCL-2 mRNAs in six fresh samples of CGCL and six fresh samples of PGCL by qRT-PCR (quantitative reverse transcription PCR) and used immunohistochemistry to demonstrate the localization of these proteins, as well as caspase 3 active in six paraffin-embedded samples of CGCL and nine paraffin-embedded samples of PGCL. While both groups showed increased expression of BAX and BCL-2 mRNA, PGCL showed a higher apoptotic index (ratio BAX/BCL-2) than CGCL. The three proteins investigated were expressed almost exclusively in the cytoplasm of giant cells. To further confirm apoptotic activity, we performed TUNEL analysis in the same samples of the immunohistochemistry and found a higher positivity in the giant cells of PGCL compared to the giant cells of CGCL. Our results show increased expression of apoptotic-related genes in both PGCL and CGCL and that the giant cells are probably the main source of these events. Also, it raises a hypothesis that differences in the apoptotic activity might be associated with the different clinical behavior of CGCL and PGCL.
颌骨中央巨细胞病变（CGCL）和外周巨细胞病变（PGCL）的特征是在单核细胞背景中存在多核破骨细胞样巨细胞。虽然在这两种病变中单核细胞都保留增殖活性，但巨细胞Ki-67呈阴性。这一观察结果提出了巨细胞由单核细胞的细胞质融合形成的理论，以及这些病变具有反应性的理论。由于巨细胞在CGCL和PGCL中不增殖，因此应该研究此类细胞的凋亡。我们通过定量逆转录PCR（qRT-PCR）研究了6个CGCL新鲜样本和6个PGCL新鲜样本中BAX和BCL-2 mRNA的转录情况，并使用免疫组织化学来证明这些蛋白的定位，以及在6个CGCL石蜡包埋样本和9个PGCL石蜡包埋样本中活化的半胱天冬酶3的定位。虽然两组均显示BAX和BCL-2 mRNA表达增加，但PGCL的凋亡指数（BAX/BCL-2比值）高于CGCL。所研究的三种蛋白几乎仅在巨细胞的细胞质中表达。为了进一步证实凋亡活性，我们在免疫组织化学的相同样本中进行了TUNEL分析，发现PGCL巨细胞中的阳性率高于CGCL巨细胞。我们的结果表明，PGCL和CGCL中凋亡相关基因的表达均增加，并且巨细胞可能是这些事件的主要来源。此外，这还提出了一个假设，即凋亡活性的差异可能与CGCL和PGCL不同的临床行为有关。
