Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma
Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma
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DOI：
10.1038/modpathol.2009.126
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发表时间：
2009-12-01
期刊：
影响因子：
7.5
通讯作者：
Inagaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakayama, Takahisa;Miyabe, Satoru;Inagaki, Hiroshi
黏液表皮样癌是唾液腺最常见的原发性恶性肿瘤。我们和其他人发现CRTC1-MAML2基因融合与有利的临床病理肿瘤特征相关。最近，一种新的基因融合，CRTC3-MAML2，被报道为在一例粘液表皮样癌中罕见的基因改变。然而，其频率和临床病理意义尚不清楚。我们共分析了101例涎腺粘液表皮样癌和89例非粘液表皮样癌，并从福尔马林固定、石蜡包埋的标本中提取RNA。在CRTC家族中，有三个基因，CRTC1， CRTC2和CRTC3。我们对CRTC1-MAML2、CRTC2-MAML2和CRTC3-MAML2融合物进行了逆转录聚合酶链反应（RT-PCR）检测。临床病理资料来源于患者的临床记录。101例粘液表皮样癌中，CRTC1-MAML2和CRTC3-MAML2融合转录物阳性分别为34例（34%）和6例（6%）。然而，在89例非黏液表皮样癌中，没有记录到这两种转录。在前一种情况下，CRTC1-MAML2和CRTC3-MAML2融合是相互排斥的。另一种融合CRTC2-MAML2未检测到。我们证实crtc1 - maml2阳性的黏液表皮样癌的临床病理特征显示为惰性过程。crtc3 - maml2阳性的黏液表皮样癌也具有临床病理优势；所有病例均表现为临床分期较轻，淋巴结转移阴性，无高级别肿瘤组织学，手术切除肿瘤后无复发或肿瘤相关死亡。有趣的是，CRTC1-MAML2阳性肿瘤患者（平均36岁）明显比CRTC1-MAML2融合患者（55岁）和融合阴性肿瘤患者（58岁）年轻。综上所述，CRTC3-MAML2融合与CRTC1-MAML2融合互斥且特异性于黏液表皮样癌，可能比之前预期的更频繁地被检测到。具有CRTC1-MAML2融合的粘液表皮样癌可能具有良好的临床病理特征，患者可能比具有CRTC1-MAML2融合或未检测到基因融合的患者年轻。现代病理学（2009）22,1575-1581；doi: 10.1038 / modpathol.2009.126;2009年9月11日在线发布
Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. We and others showed that CRTC1-MAML2 gene fusion was associated with favorable clinicopathological tumor features. Recently, a novel gene fusion, CRTC3-MAML2, was reported as a rare gene alteration in a case of mucoepidermoid carcinoma. However, its frequency and clinicopathological significance remains unclear. In all, 101 cases of mucoepidermoid carcinoma and 89 cases of non-mucoepidermoid carcinoma of the salivary gland were analyzed, and RNA was extracted from formalin-fixed, paraffin-embedded specimens. In the CRTC family, there have been three genes, CRTC1, CRTC2, and CRTC3. We developed reverse transcription-polymerase chain reaction (RT-PCR) assays for CRTC1-MAML2, CRTC2-MAML2, and CRTC3-MAML2 fusions. Clinicopathological data of the patients were obtained from their clinical records. Of 101 cases of mucoepidermoid carcinoma, 34 (34%) and 6 (6%) were positive for CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts. However, in the 89 cases of non-mucoepidermoid carcinoma, neither transcript was noted. In the former cases, CRTC1-MAML2 and CRTC3-MAML2 fusions were mutually exclusive. The other fusion, CRTC2-MAML2, was not detected. We confirmed that the clinicopathological features of CRTC1-MAML2-positive mucoepidermoid carcinomas indicated an indolent course. CRTC3-MAML2-positive mucoepidermoid carcinomas also had clinicopathologically favorable features; all cases showed a less advanced clinical stage, negative nodal metastasis, no high-grade tumor histology, and no recurrence or tumor-related death after surgical resection of the tumor. It is interesting to note that patients with CRTC3-MAML2-positive tumors (mean 36 years of age) were significantly younger that those with the CRTC1-MAML2 fusion (55 years) and those with fusion-negative tumors (58 years). In conclusion, CRTC3-MAML2 fusion, which is mutually exclusive with CRTC1-MAML2 fusion and specific to mucoepidermoid carcinoma, may be detected more frequently than previously expected. Mucoepidermoid carcinomas possessing CRTC3-MAML2 fusion may be associated with favorable clinicopathological features and patients may be younger than those with CRTC1-MAML2 fusion or those with no detectable gene fusion. Modern Pathology (2009) 22, 1575-1581; doi:10.1038/modpathol.2009.126; published online 11 September 2009