Siar Chong Huat, Nagatsuka Hitoshi, Chuah Kee Seng, Rivera Rosario Santos, Nakano Keisuke, Ng Kok Han, Kawakami Toshiyuki
Department of Oral Pathology, Oral Medicine, and Periodontology, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Aug;110(2):224-33. doi: 10.1016/j.tripleo.2010.03.009.
Notch signaling has been implicated in cell fate decisions during odontogenesis and tumorigenesis of some odontogenic neoplasms; however, its role in solid/multicystic (SA), unicystic (UA), and recurrent (RA) ameloblastoma remains unclear. The aim of this study was to determine Notch receptor and ligand expressions in these subtypes and to speculate on their significance.
Notch receptors (Notch1, 2, 3, 4) and ligands (Jagged1, 2, and Delta1) were examined immunohistochemically in SA (n = 23), UA (n = 22), and RA (n = 19).
Notch4 overexpression in SA (n = 19/23; 82.6%) compared with UA (n = 1/22; 4.5%) or RA (n = 10/19; 52.6%) (P < .05) suggests positive correlation between Notch4 signaling and ameloblastomas with a solid/multicystic phenotype. Ligand (Jagged1 and Delta1) underexpression compared with their receptors (Notch1, 3, 4) (P < .05) and nonreactivity for Notch2 and Jagged2 in all 3 subsets suggests that ameloblastoma epithelium belongs to an earlier stage of differentiation (equivalent to inner enamel epithelium of developing tooth germ) before lineage commitment.
Present findings suggest that Notch signaling molecules may play differing roles in the acquisition of different ameloblastoma phenotypes.
Notch信号通路参与牙胚发育过程中的细胞命运决定以及某些牙源性肿瘤的发生;然而,其在实性/多囊型(SA)、单囊型(UA)和复发性(RA)成釉细胞瘤中的作用仍不清楚。本研究旨在确定这些亚型中Notch受体和配体的表达,并推测其意义。
采用免疫组织化学方法检测SA(n = 23)、UA(n = 22)和RA(n = 19)中Notch受体(Notch1、2、3、4)和配体(Jagged1、2和Delta1)。
与UA(n = 1/22;4.5%)或RA(n = 10/19;52.6%)相比,SA中Notch4过表达(n = 19/23;82.6%)(P < 0.05),提示Notch4信号通路与具有实性/多囊型表型的成釉细胞瘤呈正相关。与受体(Notch1、3、4)相比,配体(Jagged1和Delta1)表达下调(P < 0.05),且在所有3个亚组中Notch2和Jagged2均无反应,提示成釉细胞瘤上皮在谱系定向之前属于分化的早期阶段(相当于发育中牙胚的内釉上皮)。
目前的研究结果表明,Notch信号分子在不同成釉细胞瘤表型的形成中可能发挥不同作用。