Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
Mod Pathol. 2013 Aug;26(8):1023-31. doi: 10.1038/modpathol.2013.31. Epub 2013 Mar 15.
Differential diagnosis of fibrous dysplasia and ossifying fibroma may often pose problems for pathologists. The purpose of this study was to evaluate the value of mutational analysis of the GNAS gene in differentiating these two conditions. DNA samples from patients with fibrous dysplasia (n=30) and ossifying fibroma (n=21) were collected to analyze the presence of GNAS mutations at exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. In all, 90% (27/30) of cases with fibrous dysplasia showed missense mutations of codon 201 at exon 8, with a predilection of arginine-to-histidine substitution (p.R201H, 70%) as opposed to arginine-to-cysteine substitution (p.R201C, 30%), whereas no mutation was detected at exon 9. No mutation was found in all 21 cases with ossifying fibroma. In addition, a meta-analysis of previously published reports on GNAS mutations in fibrous dysplasia and ossifying fibroma was performed to substantiate our findings. A total of 24 reports including 307 cases of fibrous dysplasia and 23 cases of ossifying fibroma were reviewed. The overall incidence of GNAS mutations in fibrous dysplasia was 86% (264/307), and the major types of mutations were also R201H (53%) and R201C (45%). No GNAS mutation was detected in all patients with ossifying fibroma. We also reported one case with uncertain diagnosis due to overlapping clinicopathological features of fibrous dysplasia and ossifying fibroma. An R201H mutation was detected in this case, thus confirming a diagnosis of fibrous dysplasia. Taken together, our findings indicate that mutational analysis of GNAS gene is a reliable adjunct to differentiate ossifying fibroma and fibrous dysplasia of the jaws.
纤维结构不良和骨化性纤维瘤的鉴别诊断常常给病理学家带来问题。本研究旨在评估 GNAS 基因突变分析在鉴别这两种疾病中的价值。收集了纤维结构不良(n=30)和骨化性纤维瘤(n=21)患者的 DNA 样本,使用聚合酶链反应和直接测序分析了外显子 8 和 9 中 GNAS 基因突变的存在,这两个先前报道的热点区域。在所有 30 例纤维结构不良病例中,有 90%(27/30)显示外显子 8 201 密码子的错义突变,偏好精氨酸-组氨酸取代(p.R201H,70%)而非精氨酸-半胱氨酸取代(p.R201C,30%),而在外显子 9 未检测到突变。在所有 21 例骨化性纤维瘤病例中均未发现突变。此外,对先前发表的关于纤维结构不良和骨化性纤维瘤 GNAS 突变的报告进行了荟萃分析,以证实我们的发现。共回顾了 24 份报告,包括 307 例纤维结构不良和 23 例骨化性纤维瘤病例。纤维结构不良中 GNAS 突变的总发生率为 86%(264/307),主要突变类型也是 R201H(53%)和 R201C(45%)。所有骨化性纤维瘤患者均未检测到 GNAS 突变。我们还报告了一例由于纤维结构不良和骨化性纤维瘤的临床病理特征重叠而诊断不确定的病例。该病例检测到 R201H 突变,从而确认了纤维结构不良的诊断。综上所述,我们的研究结果表明,GNAS 基因突变分析是鉴别颌骨骨化性纤维瘤和纤维结构不良的可靠辅助手段。