Xu S S, Wang L M, Zhao L H, He Z L, Gong L P, Lu D H, Teng L H
Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Department of Pathology, Capital Medical University, Beijing 100069, China.
Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Zhonghua Bing Li Xue Za Zhi. 2019 Sep 8;48(9):682-687. doi: 10.3760/cma.j.issn.0529-5807.2019.09.004.
To investigate the clinicopathological significance of BRAF V600E and CTNNB1 gene mutations in adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). The retrospective study included a total of 67 craniopharyngiomas diagnosed from October 2009 to August 2018 at Xuanwu Hospital, Capital Medical University. The immunohistochemical staining for β-catenin and BRAF V600E expression, Sanger sequencing of exon 3 of CTNNB1, BRAF mutation analysis by scorpions amplification refractory mutation system (ARMS) fluorescence quantitative PCR were performed. Univariate survival analysis was used to correlate with tumor recurrence. Of the 67 patients, 53 were ACPs and 14 were PCPs. Four patients underwent multiple operations and one of them presented with malignant transformation into squamous cell carcinoma. Histologically, ACPs were characterized by whorl-like cell clusters, peripheral palisaded layer, stellate reticulum, finger-shaped protrusions, ghost cells and wet keratinous substances. While PCPs usually consisted of mature squamous epithelium associated with fibrovascular stroma resulting in papillary appearance. The nuclear immunopositivity for β-catenin was observed in 73.6% (39/53) of ACPs, and it was absent in PCPs (0/14). The nuclear translocation of β-catenin usually presented at whorl-like structures or around ghost cells. Of all the cases, mutations analysis in exon 3 of β-catenin gene CTNNB1 were successful in 46 cases and 42.1% (16/38) of ACP showed CTNNB1 gene mutation, while none of the PCPs harbored CTNNB1 gene mutation (0/8). The cytoplasmic immunopositivity for BRAF V600E mutant protein was found in all PCPs (14/14) and negative in all ACPs (0/53). ARMS-PCR results showed that BRAF V600E mutations were observed in 13/14 of PCPs but not seen in ACPs (0/53). Follow-up data were available in 35 patients with duration of 2 to 120 months. Ten patients experienced recurrences after the first surgery. Upon univariate survival analysis, only subtotal excision was found to be associated with increased recurrence (0.032), while pathological type, postoperative radiotherapy and CTNNB1 gene mutation were not (>0.05). There is significant difference in the expression of BRAF V600E and CTNNB1 genes between ACP and PCP, and their immunohistochemical and molecular detection therefore can be used in the diagnosis and differential diagnoses of craniopharyngiomas.
探讨BRAF V600E和CTNNB1基因突变在成釉细胞瘤型颅咽管瘤（ACP）和乳头型颅咽管瘤（PCP）中的临床病理意义。这项回顾性研究共纳入了2009年10月至2018年8月在首都医科大学宣武医院诊断的67例颅咽管瘤。进行了β-连环蛋白和BRAF V600E表达的免疫组织化学染色、CTNNB1第3外显子的桑格测序、蝎形扩增不应突变系统（ARMS）荧光定量PCR检测BRAF突变。采用单因素生存分析来关联肿瘤复发情况。67例患者中，53例为ACP，14例为PCP。4例患者接受了多次手术，其中1例发生了向鳞状细胞癌的恶性转化。组织学上，ACP的特征为漩涡状细胞团、周边栅栏状层、星状网状结构、指状突起、影细胞和湿角质物质。而PCP通常由与纤维血管基质相关的成熟鳞状上皮组成，形成乳头状外观。在73.6%（39/53）的ACP中观察到β-连环蛋白的核免疫阳性，而在PCP中未观察到（0/14）。β-连环蛋白的核易位通常出现在漩涡状结构或影细胞周围。在所有病例中，β-连环蛋白基因CTNNB1第3外显子的突变分析在46例中成功，42.1%（16/38）的ACP显示CTNNB1基因突变，而PCP中无一例携带CTNNB1基因突变（0/8）。在所有PCP（14/14）中发现BRAF V600E突变蛋白的胞质免疫阳性，而在所有ACP（0/53）中为阴性。ARMS-PCR结果显示，13/14的PCP中观察到BRAF V600E突变，而ACP中未观察到（0/53）。35例患者有随访数据，随访时间为2至120个月。10例患者在首次手术后复发。单因素生存分析显示，仅次全切除与复发增加相关（0.032），而病理类型、术后放疗和CTNNB1基因突变则无相关性（>0.05）。ACP和PCP之间BRAF V600E和CTNNB1基因的表达存在显著差异，因此它们的免疫组织化学和分子检测可用于颅咽管瘤的诊断和鉴别诊断。
