Zhang X, Bai Q M, Yao Q L, Ji G, Chang H, Han J, Li Y, Ji Y, Hou Y Y, Zhou X Y
Department of Pathology, Fudan University Zhongshan Hospital, Shanghai 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Zhonghua Bing Li Xue Za Zhi. 2021 Aug 8;50(8):891-898. doi: 10.3760/cma.j.cn112151-20210421-00308.
To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC). Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed. The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all <0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival (<0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.
探讨原发性肺黏液表皮样癌（PMEC）中MAML2基因重排、基因融合模式及临床病理特征。收集2017年至2020年期间复旦大学附属中山医院和复旦大学附属肿瘤医院的46例原发性PMEC病例。采用荧光原位杂交（FISH）检测所有病例的MAML2基因重排。对其中20例采用靶向RNA测序（RNAseq）检测MAML2融合模式。分析MAML2基因重排、融合模式、临床病理特征与预后的关系。PMEC患者的平均年龄为41岁（范围15 - 71岁）；男女比例约为1.1∶1.0。大多数PMEC在组织病理学上为低级别，临床分期较早（Ⅰ - Ⅱ期）。FISH检测MAML2基因重排的总体阳性率约为80.4%（37/46），在低级别PMEC中该率更高（91.7%，33/36）。在RNAseq检测的20例中，19例FISH阳性病例均显示基因融合，主要为CRTC1 - MAML2融合（16/19），另外3例为CRTC3 - MAML2融合（3/19），所有融合模式的断点均为CRTC1/3（外显子1）- MAML2（外显子2）；单例FISH阴性病例未检测到基因融合；与MAML2 FISH阴性患者相比，携带CRTC1 - MAML2融合的PMEC在年龄≤40岁、最大肿瘤直径≤2 cm、组织病理学低级别及临床早期的患者中更常见（均<0.05）；3例携带CRTC3 - MAML2融合基因的PMEC均为女性且临床分期较早；单因素分析显示MAML2基因重排/融合、发病年龄≤40岁、肿瘤较小、组织病理学低级别、临床早期、诊断时无转移及手术治疗与总生存显著相关（<0.05），但Cox回归分析提示上述指标均不是PMEC生存的独立预后因素。PMEC中MAML2基因重排的高发生率表明它是PMEC的重要分子诊断标志物。RNAseq证实CRTC1/3 - MAML2是PMEC中的主要融合模式，提示MAML2融合转录可能是PMEC的重要驱动因素。MAML2重排/融合及相关临床病理特征与良好预后相关。
