Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Cancer Sci. 2013 Jan;104(1):85-92. doi: 10.1111/cas.12039. Epub 2012 Nov 8.
CRTC1-MAML2 and CRTC3-MAML2 fusions have been associated with favorable clinicopathological features of mucoepidermoid carcinomas. However, the significance of the MAML2 gene split has not been fully clarified. In the present study, 95 mucoepidermoid carcinomas (paraffin-embedded materials) were analyzed for CRTC1-MAML2 and CRTC3-MAML2 fusions by RT-PCR and for the MAML2 gene split by FISH. Quantitative RT-PCR for the CRTC1-MAML2 transcript was performed in selected cases. MLL gene involvement, which has been reported in some leukemia cases, was examined by FISH in fusion partner-unknown cases. CRTC1-MAML2 and CRTC3-MAML2 fusions were detected in 37 and 6 cases, respectively. The MAML2 gene split was detected in 62 cases, which included all CRTC1/3-MAML2 fusion-positive cases. The level of CRTC1-MAML2 transcript expression was highly variable, and its clinicopathological impact was unclear. The MLL gene split was not detected. Mucoepidermoid carcinomas negative for CRTC1/3-MAML2 and positive for the MAML2 gene split (n = 19) showed favorable clinicopathological tumor features similar to those positive for CRTC1/3-MAML2 fusions. Compared with negative cases (n = 33), mucoepidermoid carcinomas positive for the MAML2 split (n = 62) were associated with lower patient age, a mild female predilection, a smaller tumor size, less frequent nodal metastasis, a lower clinical stage, a lower histological grade, and longer overall and disease-free survival. The MAML2 gene split emerged as an independent prognostic factor for both overall and disease-free survival in multivariate prognostic analysis. The presence of the MAML2 gene split defines a distinct mucoepidermoid carcinoma subset that is associated clinicopathologically with favorable tumor features.
CRTC1-MAML2 和 CRTC3-MAML2 融合已与黏液表皮样癌有利的临床病理特征相关。然而，MAML2 基因分裂的意义尚未完全阐明。本研究通过 RT-PCR 分析了 95 例黏液表皮样癌（石蜡包埋材料）的 CRTC1-MAML2 和 CRTC3-MAML2 融合，并通过 FISH 分析了 MAML2 基因分裂。在选定病例中进行了 CRTC1-MAML2 转录物的定量 RT-PCR。在融合伙伴未知的病例中，通过 FISH 检查了已在一些白血病病例中报道的 MLL 基因参与情况。CRTC1-MAML2 和 CRTC3-MAML2 融合分别在 37 例和 6 例中检测到。在 62 例中检测到 MAML2 基因分裂，其中包括所有 CRTC1/3-MAML2 融合阳性病例。CRTC1-MAML2 转录物表达水平高度可变，其临床病理影响尚不清楚。未检测到 MLL 基因分裂。CRTC1/3-MAML2 阴性但 MAML2 基因分裂阳性的黏液表皮样癌（n=19）表现出与 CRTC1/3-MAML2 融合阳性病例相似的有利临床病理肿瘤特征。与阴性病例（n=33）相比，MAML2 分裂阳性的黏液表皮样癌（n=62）患者年龄较小，女性偏好较轻，肿瘤体积较小，淋巴结转移较少，临床分期较低，组织学分级较低，总生存期和无病生存期较长。在多变量预后分析中，MAML2 基因分裂是总生存期和无病生存期的独立预后因素。MAML2 基因分裂的存在定义了一个独特的黏液表皮样癌亚组，与临床病理上有利的肿瘤特征相关。
