Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, MD 21231, USA.
Hum Pathol. 2012 Apr;43(4):585-91. doi: 10.1016/j.humpath.2011.06.009. Epub 2011 Sep 21.
A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P = .03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.
对导管内乳头状黏液性肿瘤（IPMN）进行更好的分子特征分析，可能对其早期检测和制定有效的治疗策略具有关键作用，IPMN 是胰腺腺癌最常见的囊性前体病变。BRG1 是调节转录的染色质重塑复合物 SWI/SNF 的核心组成部分，在几种恶性肿瘤中失活。在这项研究中，我们评估了导管内乳头状黏液性肿瘤中 Brg1 的表达，以更好地了解其在胰腺发生癌变中的作用。对 66 例手术切除的 IPMN 组织微阵列进行 Brg1 蛋白免疫标记，然后将表达模式与临床病理参数相关联。正常胰腺上皮强烈免疫标记为 Brg1。在 60 例可评估的 IPMN 病变中，有 32 例（53.3%）观察到 Brg1 表达减少，并且在高级别 IPMN 中更为常见（17 例中有 13 例显示缺失；76%），与中级别（29 例中有 15 例显示缺失；52%）和低级别 IPMN（14 例中有 4 例显示缺失；28%）相比（P =.03）。在 60 个病变中有 5 个（8.3%）完全丧失 Brg1 表达。最后，通过 Western blot 分析，还在低传代的非浸润性 IPMN 细胞系中观察到 Brg1 蛋白表达减少。我们没有观察到 Brg1 表达与 IPMN 亚型或囊肿位置之间的相关性。我们首次提供证据表明，BRG1 表达在胰腺腺癌的非浸润性囊性前体病变中丢失。
