Acinar cell carcinomas of the pancreas: a molecular analysis in a series of 57 cases
Acinar cell carcinomas of the pancreas: a molecular analysis in a series of 57 cases
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DOI：
10.1007/s00428-014-1657-8
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发表时间：
2014-12-01
期刊：
影响因子：
3.5
通讯作者：
Blaeker, Hendrik
中科院分区：
文献类型：
--
作者：
Bergmann, Frank;Aulmann, Sebastian;Blaeker, Hendrik
胰腺腺泡细胞癌（PAC）是一种罕见的侵袭性肿瘤，其表型不同于胰腺导管腺癌（PDAC）和胰腺神经内分泌肿瘤（PNEN）。尽管最近的工作对PAC的遗传变化，其分子发病机制仍然知之甚少。在这项研究中，我们专注于比较基因组杂交分析。基于频繁的染色体失衡，进一步研究DCC和c-MYC在PAC发病机制中的参与。此外，我们检查了具有潜在治疗相关性的标志物（K-RAS、BRAF、EGFR、MGMT、HSP 90、L1 CAM、Her 2）。PAC揭示了微卫星稳定，染色体不稳定的基因型，其定义为1 p，3 p，4 q，5 q，6 q，8 p，9 p，11 q，13 q，16 q和18的反复染色体丢失，以及1 q，7，8 q，12，17 q和20 q的增加。PAC亚组显示DCC（79%）和c-MYC扩增（17%）减少/丧失。42%的患者EGFR表达明显，98%的患者HSP 90表达明显，72%的患者L1 CAM表达明显，26%的患者MGMT缺失。2例携带K-RAS突变。未检测到EGFR或BRAF突变。所有病例均为Her 2/neu阴性。PAC显示特征性染色体不平衡，这与胰腺导管腺癌和胰腺神经内分泌肿瘤明显不同。我们的研究结果表明，DCC和c-MYC的改变可能在PAC的发病机制中发挥重要作用。此外，EGFR、MGMT、HSP 90和L1 CAM可用作PAC亚组中的治疗标志物和治疗应答的预测因子。
Pancreatic acinar cell carcinomas (PACs) are rare but are distinct aggressive neoplasms that phenotypically differ from pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine neoplasms (PNENs). Despite recent work on the genetic changes of PACs, their molecular pathogenesis is still poorly understood. In this study, we focus on a comparative genomic hybridization analysis. Based on frequent chromosomal imbalances, the involvement of DCC and c-MYC in the pathogenesis of PACs is further investigated. Moreover, we examine markers harboring potential therapeutic relevance (K-RAS, BRAF, EGFR, MGMT, HSP90, L1CAM, Her2). PACs revealed a microsatellite stable, chromosomal unstable genotype, defined by recurrent chromosomal losses of 1p, 3p, 4q, 5q, 6q, 8p, 9p, 11q, 13q, 16q, and 18, as well as gains of 1q, 7, 8q, 12, 17q, and 20q. Subsets of PAC displayed reduction/loss of DCC (79 %) and c-MYC-amplification (17 %). Significant EGFR expression occurred in 42 %, HSP90 expression in 98 %, L1CAM expression in 72 %, and loss of MGMT in 26 %. Two cases carried a K-RAS mutation. Mutations of EGFR or BRAF were not detected. All cases were Her2/neu-negative. PACs display characteristic chromosomal imbalances which are distinctly different from those in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms. Our findings suggest that DCC and c-MYC alterations may play an important role in the pathogenesis of PACs. Furthermore, EGFR, MGMT, HSP90, and L1CAM may be useful as therapeutic markers and predictors of response to therapy in a subset of PACs.